CHANNELS, RECEPTORS, AND ELECTRICAL SIGNALING |
Cav1.4 encodes a calcium channel with low open probability and unitary conductance
Clinton J Doering 1, Jawed Hamid 1, Brett A Simms 1, John E McRory 1 and Gerald W Zamponi 1*
1 University of Calgary
* To whom correspondence should be addressed. E-mail: zamponi{at}ucalgary.ca.
Submitted on May 22, 2005
Revised on June 21, 2005
Accepted on 19 July 2005
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Abstract |
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When transiently expressed in tsA-201 cells, Cav1.4 calcium channels support only modest whole-cell currents with unusually slow voltage-dependent inactivation kinetics. To determine the basis for this unique behavior we used cell attached patch single channel recordings using 100 mM external barium as the charge carrier to determine the single channel properties of Cav1.4 and to compare them to those of the Cav1.2. Cav1.4 channel openings occurred infrequently and were of brief duration. Moreover, openings occurred throughout the duration of the test depolarization, indicating that the slow inactivation kinetics observed at the whole-cell level are caused by sustained channel activity. Cav1.4 and Cav1.2 channels displayed similar latencies to first opening. Because of the rare occurrence of events, the probability of opening could not be precisely determined but was estimated to be smaller than 0.015 over a voltage range of -20 mV to +20 mV. The single channel conductance of Cav1.4 channels was ~4 pS compared with ~20 pS for Cav1.2 under the same experimental conditions. Additionally, in the absence of divalent cations, Cav1.4 channels pass cesium ions with a single channel conductance of ~21 pS. While Cav1.2 opening events were best described kinetically with two open time constants, Cav1.4 open times were best described by a single time constant. BayK8644 slightly enhanced the single channel conductance in addition to increasing the open time constant for Cav1.4 channels by about 45% without, however, causing the appearance of an additional slower gating mode. Overall, our data indicate single Cav1.4 channels support only minute amounts of calcium entry, suggesting that large numbers of these channels are needed to allow for significant whole-cell current activity, thus providing a mechanism to reduce noise in the visual system.
Key Words:
BayK8644, Cav1.4, L-type channel, alpha 1F, photoreceptors, single channel
