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Biophys J, October 1999, p. 1905-1913, Vol. 77, No. 4
*Vollum Institute and #Department of Obstetrics and Gynecology, Oregon Health Sciences University, Portland, Oregon 97201 USA
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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The activation of small-conductance calcium-activated potassium channels (SK) has a profound effect on membrane excitability. In hippocampal pyramidal neurons, SK channel activation by Ca2+ entry from a preceding burst of action potentials generates the slow afterhyperpolarization (AHP). Stimulation of a number of receptor types suppresses the slow AHP, inhibiting spike frequency adaptation and causing these neurons to fire tonically. Little is known of the gating properties of native SK channels in CNS neurons. By using excised inside-out patches, a small-amplitude channel has been resolved that was half-activated by ~0.6 µM Ca2+ in a voltage-independent manner. The channel possessed a slope conductance of 10 pS and exhibited nonstationary gating. These properties are in accord with those of cloned SK channels. The measured Ca2+ sensitivity of hippocampal SK channels suggests that the slow AHP is generated by activation of SK channels from a local rise of intracellular Ca2+.
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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The slow afterhyperpolarization (AHP) in
hippocampal neurons has an important influence on membrane
excitability. It is activated after a burst of action potentials and
underlies spike frequency adaptation, terminating burst firing (Madison
and Nicoll, 1984
). The slow AHP is generated by activation of small
conductance calcium-activated potassium channels (SK), resulting from
the entry of Ca2+ through voltage-gated Ca2+
channels (Lancaster and Nicoll, 1987). It has been assumed that multiple SK channels may exist because the AHP in some cell types is
sensitive to the bee venom toxin, apamin (e.g., bullfrog sympathetic neurons, Pennefather et al., 1985) and is not in others (e.g., rat hippocampal CA1 pyramidal neurons, Lancaster and Adams, 1986). This
assumption has been confirmed by the cloning of three distinct members
of the SK channel family, SK1-3 (Köhler et al., 1996; Joiner et
al., 1997). Both the apamin-insensitive SK1 and the apamin-sensitive
SK2 channels exhibited a single channel conductance of ~10 pS in
isotonic potassium and were half-activated by 0.6-0.7 µM
Ca2+ (Köhler et al., 1996; Hirschberg et al., 1998).
These data are in agreement with the single SK channel properties
observed in GH3 anterior pituitary cells (Lang and Ritchie,
1987), T lymphocytes (Grissmer et al., 1992), and adrenal chromaffin
cells (Park, 1994). However, the only study of single SK channels in
hippocampal pyramidal neurons reported a larger single channel
conductance of 18-20 pS and a slightly lower sensitivity to
Ca2+ [open probability (Po)
0.5 with 1 µM Ca2+; designated P(o) in figures]
(Lancaster et al., 1991).
A significantly greater Ca2+ sensitivity of SK channels
might be expected from intracellular Ca2+ imaging studies
in hippocampal neurons, since it has been shown that during the slow
AHP the somatic Ca2+ concentration increases only to 0.1 µM (Knöpfel et al., 1990). However, the
Po of SK channels at the peak of the slow AHP
has been estimated to be 0.4-0.6 (Sah and Issacson, 1995; Valiante et
al., 1997), predicting an intracellular Ca2+ concentration
of 0.5-1 µM. It is possible that neither the channel described
previously in hippocampal neurons (Lancaster et al., 1991) nor a
homolog of the recombinant SK1-3 underlies the slow AHP in hippocampal
neurons. Alternatively, hippocampal SK channels may only be activated
by local increases in Ca2+ that are not reflected by the
somatic measurements.
We have examined the gating properties of the hippocampal SK channel.
By using inside-out membrane patches excised from acutely isolated
hippocampal CA1 pyramidal neurons, we have determined that hippocampal
SK channels exhibit a conductance of 10 pS (in symmetrical potassium
solutions), are half-activated by ~0.6 µM Ca2+, and
display voltage-independent gating. In addition, hippocampal SK
channels display nonstationary kinetics. These properties are very
similar to cloned rSK2 and hSK1 channels (Köhler et al., 1996;
Hirschberg et al., 1998) and suggest that activation of SK channels
underlying generation of the slow AHP occurs by a local rise of
submembrane Ca2+ to levels higher than those measured in
the soma.
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MATERIALS AND METHODS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Acutely dissociated hippocampal CA1 neurons were obtained as
described previously (Cloues et al., 1997). Briefly, Sprague-Dawley rats (9-14 days old) were anesthetized with halothane and decapitated. Hippocampi were rapidly dissected and cut into 300-400-µm slices. Slices were incubated at 37°C in a dissociation solution containing (in mM): Na2SO4, 82;
K2SO4, 30; HEPES, 10; MgCl2, 5;
ethylene glycol bis (b-aminoethyl ether)-N,
N,N',N'-tetraacetic acid (EGTA), 1 (pH 7.4), with added protease
type XXIII (3 mg/ml) for 7-8 min and bubbled with O2.
Tissue slices were then transferred to a solution containing trypsin
inhibitor (1 mg/ml) and bovine serum albumin (BSA) (1 mg/ml) for 1 min
and finally rinsed in dissociation solution containing no enzyme. The
CA1 region was microdissected and triturated into Falcon Primaria
dishes as needed.
Cells were washed and superfused (15 ml min
1) with an
external solution containing (in mM): KMeSO4, 125; KCl, 35;
HEPES(Na), 10; EGTA, 10; CaCl2, 5.64 (to give an estimated
free concentration of 0.06 µM (Fabiato and Fabiato, 1979) (pH 7.4 with KOH). Cells in this solution had ~0 mV membrane potential. All
potentials are expressed as the negative of the potential imposed on
the pipette. Membrane patches were first excised to the inside-out patch configuration into the Mg2+-free superfusion solution
containing 0.1 µM Ca2+. The free Ca2+
concentration was raised up to 3 µM (Fabiato and Fabiato, 1979) once
the patch had stabilized. Changes in solutions containing different
concentrations of free Ca2+ were achieved by bath
superfusion and were complete within several seconds.
Excised inside-out patch recordings (Hamill et al., 1981) were made
using thick-walled (1.5 mm O.D., 0.5 mm I.D.) quartz electrodes (7-10
M
) containing the external solution described above, supplemented with 100 nM charybdotoxin to prevent contamination by BK channel openings. Voltage-dependent potassium channel activity was prevented by
including 4-aminopyridine (1 mM), 3,4-diaminopyridine (1 mM), 
-dendrotoxin (200 nM), and 
-dendrotoxin (200 nM) in the pipette solution. Single channel currents were recorded with an Axopatch 200 amplifier using a CV201A headstage (Axon Instruments, Foster City, CA),
filtered at 1-4 kHz with an 8-pole Bessel filter (Frequency Devices,
Haverhill, MA) and acquired at 100-µs intervals for analysis using
Pulse (Heka, dist. by Instrutech Corp., New York, NY) onto a Quadra 650 (Apple Computer, Cupertino, CA). No differences in open and closed
times were seen when data were filtered either at 1 kHz or 4 kHz.
Single channels were analyzed using MacTAC (Bruxton Corp., Seattle, WA,
dist. by Instrutech Corp., NY). The "50% threshold" technique was
used to estimate event amplitudes and durations, with each transition
inspected visually before being accepted. Open and closed duration
histograms were constructed with MacTacfit (Bruxton Corp., distributed
by Instrutech Corp.), binned logarithmically (20 bins/decade) and
plotted against the square root transformation of the ordinate (number
of events/bin). The distribution was fitted by a sum of exponential
probability density functions using the maximum-likelihood method. With
this type of representation, peaks in the histogram correspond to the time constant of the exponential (Sigworth and Sine, 1987). A correction was made for the rise time of the filter (Colquhoun and
Sigworth, 1983) and all bins were used for fitting. The number of
statistically significant components was determined by the method of
maximum likelihood ratios (Horn and Lange, 1983). Data were not
corrected for missed events. Channel open probability (Po) was estimated as
NPo, the product of the open probability times
the number of channels. NPo was calculated using
ReadEvents v1.37 (Scott Eliasof, Portland, OR), as the sum of (dwell
time × level number) divided by the total time. N was
estimated as the number of simultaneously open channels at a
Po > 0.5. Finally, Po was obtained by dividing
NPo by N. Where applicable, values were expressed as mean ± SD, and P values were derived
from unpaired two-tailed Student's t-tests. Results were
considered significantly different at P < 0.01. Oocyte
expression and recordings of cloned hSK1 channels were performed as
described previously for rSK2 (Hirschberg et al., 1998).
We observed a variable degree of channel "run-down" in the absence
of any treatment. In the presence of a fixed concentration of
Ca2+, ~30% of patches exhibited SK channels whose
activity was lost within the first minute of recording. Of the
remaining patches, ~70% exhibited SK channels whose activity was
lost within the first 10 min of recording. Loss of activity occurred
during high and low Po behavior and was abrupt,
complete, and irreversible; i.e., no channel openings were observed
over minutes even in increased [Ca2+] or after removal
and reapplication of Ca2+. Generally, there was no change
in gating leading up to the loss of activity. The loss of SK channel
activity in excised inside-out patches may suggest that channel
activity requires cytoplasmic factors. All reagents were obtained from
Sigma, except - and -dendrotoxin (Alomone, Israel),
CaCl2 (Fluka, NY), and HEPES (Calbiochem, CA).
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Ca2+- and voltage-dependence of hippocampal SK channels
In ~90 of 600 patches, application of Ca2+ to the
inner face of inside-out membrane patches caused activation of a
small-amplitude channel. Increasing the concentration of
Ca2+ from 0.1 to 1 µM caused a progressive increase in
channel Po (Fig. 1
A). A plot of Po as a function of
Ca2+ concentration was described by the Hill equation, with
an EC50 of 0.56 µM and a Hill coefficient
(nH) of 4.6 (Fig. 1 B). This observed
Ca2+-dependence of channel Po agrees
well with the macroscopic Ca2+-dependence of both hSK1 and
rSK2 (EC50 values 0.7 and 0.63 µM and
nH values of 3.9 and 4.8, respectively;
Köhler et al., 1996).
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The voltage-dependence of channel Po was
determined in the presence of a fixed Ca2+ concentration.
Fig. 2 A shows traces from a
patch recorded at three membrane potentials containing a single SK
channel activated by 1 µM Ca2+. Channel gating was not
obviously dependent on membrane potential, with
Po values being similar over a membrane
potential range of 
100 to +60 mV (Fig. 2 B). Measurement
of the single channel amplitude at each voltage gave rise to the
current-voltage relationship shown (Fig. 2 B, inset),
yielding a slope conductance of 9.8 pS. Determination of slope
conductance in six patches gave a mean value of 10.1 ± 0.5 pS.
The Ca2+ sensitivity, voltage-independence, and single
channel conductance of this channel were not significantly different
from those obtained from both hSK1 and rSK2 clones (see Köhler et
al., 1996 and Hirschberg et al., 1998), identifying it as an SK
channel.
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Kinetic properties of hippocampal SK channels
SK channel gating is voltage-independent
The decay of the slow AHP in hippocampal pyramidal neurons is insensitive to membrane potential (Lancaster and Adams, 1986). This may
arise from the open-state kinetics of the underlying SK channel being
insensitive to voltage, as occurs with cloned rSK2 channels (Hirschberg
et al., 1998). In the presence of a fixed concentration of
Ca2+, the Po of hippocampal SK
channels was voltage-independent (Fig. 2 B). Fig.
3 A shows open duration
histograms at 60 mV and +60 mV constructed from a single channel
patch bathed in 1 µM Ca2+. Both open duration histograms
were best fit by the sum of two exponentials with similar time
constants (Fig. 3 A). The time constant of each exponential
component is shown as a function of membrane potential in Fig. 3,
B and C, with each symbol reflecting data from
one patch. Data from hippocampal neurons are shown as closed symbols,
and data from cloned hSK1 channels expressed in Xenopus
oocytes are shown for comparison (open symbols). The long and short open-time constants seen with hippocampal SK channels were
indistinguishable from those obtained with hSK1, and both open-time
constants were independent of voltage. In addition, voltage did not
significantly affect the relative contribution of each exponent to the
open duration histogram (Fig. 3 D).
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Two gating behaviors distinguished by open- and closed-time kinetics
rSK2 channels have been shown to exhibit and switch between two dominant modes of gating, low and high Po behavior (Hirschberg et al., 1998). The open-time distribution of rSK2
channels exhibiting either behavior was best fit by the sum of two
exponentials, with a larger fraction of short-duration events occurring
during low Po (Hirschberg et al., 1998).
However, the main factor determining the observance of low
Po was the presence and weighting of a very slow
closed-time component (Hirschberg et al., 1998). During high Po activity this closed time was absent, being
replaced by a closed time an order of magnitude faster (Hirschberg et
al., 1998).
rSK2 channels were found to switch Po behaviors
most frequently in Ca2+ concentrations close to the
EC50 (Hirschberg et al., 1998). In 8 of 10 patches
exposed to 0.6 µM Ca2+ and three of three patches
exposed to 1 µM Ca2+, hippocampal SK channels were
observed to spontaneously switch Po behaviors
during the time of recording. This is illustrated in Fig.
4. During the first 2 min of recording in
the presence of 1 µM Ca2+, a patch containing a single SK
channel exhibited relatively high Po (Fig. 4,
A and B). Analysis of open and closed times
showed that the majority of openings were of long duration (
= 6.3 and 1.2 ms), with closed times being best described by the sum of two exponentials with time constants of 0.94 and 5.7 ms (Fig. 4
C). After ~114 s of recording, SK channel activity
switched to an extremely low Po behavior (Fig.
4, A and B). Observed openings were rare and of
short duration, being described by a single exponential of time
constant 0.64 ms (Fig. 4 D, left). In contrast to high Po behavior, the closed-time distribution was
best fit by the sum of three exponentials ( = 1.7, 5.6, and 208 ms) (Fig. 4 D, right). As with cloned rSK2 channels, the
short and intermediate closed times were similar to those seen during
high Po behavior with the appearance of an
additional very long closed time. After ~60 s of low
Po behavior, SK channel activity abruptly
switched back to high Po behavior (Fig. 4,
A and B). In three patches bathed in 1 µM
Ca2+, average Po values were
0.67 ± 0.13 for the high Po behavior and
0.03 ± 0.02 for the low Po behavior.
Therefore, in the presence of a fixed concentration of
Ca2+, hippocampal SK channels can spontaneously and rapidly
switch between two Po behaviors, a property
observed with cloned rSK2 channels (Hirschberg et al., 1998).
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Ca2+-dependence of SK channel Po behavior
It has been reported that rSK2 channels spent more time in high Po activity as the Ca2+ concentration was increased (Hirschberg et al., 1998). A similar relationship was observed with hippocampal SK channels. In the presence
of 0.3 µM Ca2+, SK channel activity was of very low
Po throughout, with only brief sojourns to
an intermediate value (Fig.
5Ai). Open- and closed-time
analysis revealed that the majority of openings were of short
duration ( = 0.8 and 6.5 ms) and the closed-time distribution was best described by the sum of three exponentials ( = 1.1, 5.1, and 711 ms) (Fig. 5 Aii). Increasing the concentration
of Ca2+ bathing the patch to 3 µM evoked predominantly
high Po activity (Fig. 5 Bi). The
majority of openings were of long duration ( = 12.6 ms) with a
minor component of short-duration openings ( = 0.9 ms). Most
closures were described by exponentials with short and intermediate
time constants ( = 0.68 and 3.3 ms), with a few events of
longer time constant ( = 150 ms) corresponding to the very
brief period of low Po behavior shown in Fig. 5
Bi (asterisk; Fig. 5 Bii). Therefore,
high and low Po behaviors can be observed over a
range of Ca2+ concentrations, and raising the
Ca2+ concentration promotes high Po
SK channel gating.
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Ca2+-dependence of SK channel open and closed times
A Ca2+-dependence of the long closed time is apparent from histograms shown in Figs. 3-5. In contrast, the time constants describing channel openings were similar in different Ca2+ concentrations, and only their relative contribution varied. Hippocampal SK channel kinetics were determined over a range of 0.3 to 3 µM Ca2+, and data from cloned hSK1 channels are shown as the open symbols for comparison (Fig. 6). The open-time constant of hippocampal SK channels did not change significantly over this range of Ca2+, and was similar to that seen with hSK1 (Fig. 6, A and B). The Ca2+-dependence of channel Po was in part due to Ca2+-dependent changes in the relative fractions of long and short openings. Fig. 6 C shows that the percentage of openings described by the short time constant exponent decreased monotonically as the Ca2+ concentration was increased.
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). Therefore, the increase in SK
channel Po observed on increasing the
concentration of Ca2+ is attributed to a decrease in the
number and lifetime of long closures and an increase in the number of
long-duration openings.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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The conductance, Ca2+ sensitivity, and
voltage-independent properties of SK channels in hippocampal CA1
pyramidal neurons were very similar to those observed for cloned
apamin-sensitive rSK2 channels (Hirschberg et al., 1998). However,
hippocampal SK channels are insensitive to the bee venom toxin, apamin
(Lancaster and Adams, 1986). We have initiated a study of the
properties of the apamin-insensitive cloned hSK1 channel. We have
observed a single channel conductance of 9.2 ± 0.3 pS
(N = 3) in isotonic potassium, a value not
statistically different from that observed with hippocampal SK channels
(P > 0.01; Köhler et al., 1996). hSK1 channels
were half-activated by 0.7 ± 0.06 µM Ca2+, with an
nH value of 3.9 ± 0.45 (Köhler et
al., 1996), values very similar to hippocampal SK channels (see text).
Combining data from both Po behaviors, mean
open-time constants for hippocampal SK channels were
1 = 1.1 ± 0.3 ms and 2 = 7.7 ± 2.9 ms (N = 11), while hSK1 open times were
1 = 1.0 ± 0.4 ms and 2 = 6.5 ± 2.3 ms (N = 10). These comparisons suggest
that hippocampal SK channels may be the native correlate for the SK1
gene product. Support for this proposal comes from RT-pcr experiments
on RNA isolated from acutely dissociated rat CA1 neurons. Primers were used to sequences within the core of the molecule that were
conserved between rSK1 and hSK1, but divergent in rSK2. Control
experiments showed that these primers were indeed subtype-specific
(data not shown). These experiments show that an abundance of SK1 mRNA
is present in hippocampal CA1 neurons, with only a minor presence of
SK2 transcript (J. P. Adelman, unpublished observation). However, it should be noted that our comparison is between the SK channel native
to rat hippocampal neurons and the heterologously expressed human SK1
channel. The biophysical properties of rSK1 are not known.
The slow rise of the slow AHP in hippocampal neurons has been proposed
to arise from the diffusion of Ca2+ from its point of entry
to the SK channel (Lancaster and Adams, 1986). The main support of this
proposal is that the slow AHP can be eliminated by intracellular EGTA,
a relatively slow Ca2+ chelator (Lancaster and Nicoll,
1987). The observed sensitivity of hippocampal SK channels to
Ca2+ (EC50 0.56 µM, see Fig. 1) demands that
a substantial rise in intracellular Ca2+ concentration must
underlie generation of the slow AHP. This argument is supported by the
finding that the Po of the SK channel at the
peak of the slow AHP is 04-0.6 (Sah and Issacson, 1995; Valiante et
al., 1997), values that can only be observed with an intracellular
Ca2+ concentration of 0.6-1 µM (see Fig. 1). However,
bulk increases of intracellular Ca2+ only up to 0.1 µM
have been measured (Knöpfel et al., 1990).
The slow AHP in hippocampal neurons is blocked by nimodipine, implying
that L-type channels provide Ca2+ for SK channel activation
(Rascol et al., 1991; Moyer et al., 1992; Tanabe et al., 1998). The
subcellular location of SK channels in hippocampal neurons is not
known. It has been proposed that they may be somatic (Lancaster et al.,
1991) or located in the proximal dendritic tree (Sah and Bekkers,
1996). SK channels recorded in this study were somatic, as is the
distribution of L-type Ca2+ channels in these neurons (Hell
et al., 1993). This distribution, within a soma of ~10 µm in
diameter, appears inconsistent with the slow rise of the slow AHP. It
has been suggested that the characteristic time course of the slow AHP
results from SK channels activating slowly in response to an increase
in cytosolic Ca2+ (Sah and Clements, 1999). This was
suggested because it was assumed that SK channels are located in the
proximal apical dendrite (Sah and Bekkers, 1996) and the kinetics
of the intracellular Ca2+ transient observed in this region
are too rapid (Sah and Clements, 1999). However, this proposal assumes
that SK channels are not somatic in their distribution, contradicting
evidence from single channel recording (Lancaster et al., 1991; this
study). In addition, to permit a model to be constructed reproducing
the time course of the slow AHP, it was assumed that SK channels are
activated by Ca2+ with an EC50 of 150 nM (Sah
and Clements, 1999). This assumption is not supported by measurements
of both cloned (Köhler et al., 1996; Hirschberg et al.,
1998) and native (Lang and Ritchie, 1987; Lancaster et al., 1991;
Grissmer et al., 1992; Park, 1994; Selyanko et al., 1998; this study)
SK channels. Finally, this suggestion is not in agreement with the
rapid activation of cloned SK channels by intracellular
Ca2+ (Xia et al., 1998) and the finding in this study that
the closed-time kinetics of hippocampal SK channels are consistent with
them responding rapidly to a rise of intracellular Ca2+
(see Figs. 4-6).
Recently, L-type Ca2+ and SK channels have been observed
within the same patch. These experiments have indicated that L and SK
channels are colocalized, being separated by only ~100-150 nm
(Marrion and Tavalin, 1998). This finding is consistent with requiring
~1 µM Ca2+ to be present at the SK channel during the
peak of the slow AHP (see above). However, it does not explain the
kinetics of activation of the slow AHP. SK channels activate quite
rapidly. For example, fast-flow application of 10 µM Ca2+
to excised inside-out macropatches found that hSK1 and rSK2 channels activated with time constants of 5.8 and 6.3 ms, respectively (Xia et
al., 1998; see also Lancaster and Zucker, 1994). Modeling SK channel
gating has predicted that rSK2 channels would activate with a time
constant of ~20 ms in the presence of 1 µM Ca2+
(Hirschberg et al., 1998). Therefore, the relative proximity would
permit a high enough concentration of Ca2+ to be present at
the SK channel, but the predicted rate of activation does not allow for
a slow rise of the slow AHP. It has been proposed that delayed
facilitation of L-type Ca2+ channels underlies the time
course of the slow AHP (Cloues et al., 1997). Delayed facilitation is
induced by a train of action potential waveforms and is characterized
by prolonged L-type channel activity at membrane potentials negative to
60 mV (Cloues et al., 1997). The time course of delayed facilitation
is the same as the slow AHP, with both exhibiting a slow-rising phase
and decay (Pedarzani and Storm, 1993; Cloues et al., 1997). Therefore, it is possible that delayed facilitation dictates the time course of SK
channel activation, producing the characteristic slow rise and decay of
the slow AHP.
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ACKNOWLEDGMENTS |
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The authors thank Drs. D. Shepherd and S. J. Tavalin for helpful discussions and critical reading of the manuscript. In addition, we thank Dr. D. Shepherd for cell preparation.
This work was supported by a National Research Service Award (NRSA; to B.H.) and National Institutes of Health (NIH) Grant NS20986 (to N.V.M.).
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FOOTNOTES |
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Received for publication 23 September 1998 and in final form 16 June 1999.
Address reprint requests to Neil V. Marrion, Department of Pharmacology, University of Bristol, School of Medical Sciences, University Walk, Bristol BS8 1TD, United Kingdom. Tel.: +44-117-928-7636; Fax: +44-117-925-0168; E-mail: N.V.Marrion{at}bris.ac.uk.
Birgit Hirschberg's present address is Merck & Co., RY80N-C42, P.O. Box 2000, Rahway NJ 07065-0900.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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-Adrenergic stimulation selectively inhibits long-lasting L-type calcium channel facilitation in hippocampal neurons.
J. Neurosci.
17:6493-6503[Abstract/Full Text].1 subunits.
J. Cell. Biol.
123:949-962[Abstract].
Biophys J, October 1999, p. 1905-1913, Vol. 77, No. 4
© 1999 by the Biophysical Society 0006-3495/99/10/1905/09 $2.00
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F. Vogalis, J. B. Furness, and W. A. A. Kunze Afterhyperpolarization Current in Myenteric Neurons of the Guinea Pig Duodenum J Neurophysiol, May 1, 2001; 85(5): 1941 - 1951. [Abstract] [Full Text] [PDF]
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 P. Pedarzani, J. Mosbacher, A. Rivard, L. A. Cingolani, D. Oliver, M. Stocker, J. P. Adelman, and B. Fakler Control of Electrical Activity in Central Neurons by Modulating the Gating of Small Conductance Ca2+-activated K+ Channels J. Biol. Chem., March 23, 2001; 276(13): 9762 - 9769. [Abstract] [Full Text] [PDF]
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