This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.105.067124v1 89/5/3042    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Doering, C. J. Articles by Zamponi, G. W. Search for Related Content PubMed PubMed Citation Articles by Doering, C. J. Articles by Zamponi, G. W.

Ca_v1.4 Encodes a Calcium Channel with Low Open Probability and Unitary Conductance

Clinton J. Doering ^* , Jawed Hamid ^*, Brett Simms ^*, John E. McRory ^* and Gerald W. Zamponi ^*

^* Hotchkiss Brain Institute, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Canada; and NeuroMed Technologies, Vancouver, Canada

Correspondence: Address reprint requests to Dr. Gerald W. Zamponi or Dr. John McRory, Dept. of Physiology and Biophysics, University of Calgary, 3330 Hospital Dr. NW, Calgary, T2N 4N1 Canada. Tel.: 403-220-8687; Fax: 403-210-8106; E-mail: Zamponi{at}ucalgary.ca or Mcroryj{at}ucalgary.ca.

When transiently expressed in tsA-201 cells, Ca_v1.4 calcium channels support only modest whole-cell currents with unusually slow voltage-dependent inactivation kinetics. To examine 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 Ca_v1.4 and to compare them to those of the Ca_v1.2. Ca_v1.4 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. Ca_v1.4 and Ca_v1.2 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 <0.015 over a voltage range of –20 to +20 mV. The single-channel conductance of Ca_v1.4 channels was 4 pS compared with 20 pS for Ca_v1.2 under the same experimental conditions. Additionally, in the absence of divalent cations, Ca_v1.4 channels pass cesium ions with a single-channel conductance of 21 pS. Although Ca_v1.2 opening events were best described kinetically with two open time constants, Ca_v1.4 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 Ca_v1.4 channels by 45% without, however, causing the appearance of an additional slower gating mode. Overall, our data indicate that single Ca_v1.4 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, and providing a mechanism to reduce noise in the visual system.