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J. Gen. Physiol.,
Volume 112, Number 2, August 1, 1998 125-143
1E
Calcium Channels
From the Program in Molecular and Cellular Systems Physiology, Departments of Biomedical Engineering and Neuroscience, Johns
Hopkins University School of Medicine, Baltimore, Maryland 21205
Voltage-gated calcium channels are composed of a main pore-forming 
1 moiety, and one or more
auxiliary subunits (
, 2
) that modulate channel properties. Because modulatory properties may vary greatly with
different channels, expression systems, and protocols, it is advantageous to study subunit regulation with a uniform experimental strategy. Here, in HEK 293 cells, we examine the expression and activation gating of 1E calcium channels in combination with a (1-4) and/or the 2 subunit, exploiting both ionic- and gating-current
measurements. Furthermore, to explore whether more than one auxiliary subunit can concomitantly specify gating properties, we investigate the effects of cotransfecting 2 with subunits, of transfecting two different subunits simultaneously, and of COOH-terminal truncation of 1E to remove a second binding site. The main results are as follows. (a) The 2 and subunits modulate 1E in fundamentally different ways. The sole effect of
2 is to increase current density by elevating channel density. By contrast, though subunits also increase functional channel number, they also enhance maximum open probability (Gmax/Qmax) and hyperpolarize the voltage
dependence of ionic-current activation and gating-charge movement, all without discernible effect on activation
kinetics. Different isoforms produce nearly indistinguishable effects on activation. However, subunits produced clear, isoform-specific effects on inactivation properties. (b) All the subunit effects can be explained by a
gating model in which subunits act only on weakly voltage-dependent steps near the open state. (c) We find no
clear evidence for simultaneous modulation by two different subunits. (d) The modulatory features found here
for 1E do not generalize uniformly to other 1 channel types, as 1C activation gating shows marked isoform dependence that is absent for 1E. Together, these results help to establish a more comprehensive picture of auxiliary-subunit regulation of 1E calcium channels.
1E;
gating currents;
subunit modulation;
heterologous expression
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