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1E Calcium Channels
ABSTRACT
Voltage-gated calcium channels are composed of a main pore-forming 
1 moiety, and one or more auxiliary subunits (β, 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 β (β1–β4) 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 β subunits, of transfecting two different β subunits simultaneously, and of COOH-terminal truncation of 1E to remove a second β binding site. The main results are as follows. (a) The 2 and β subunits modulate 1E in fundamentally different ways. The sole effect of 2 is to increase current density by elevating channel density. By contrast, though β 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 β isoforms produce nearly indistinguishable effects on activation. However, β subunits produced clear, isoform-specific effects on inactivation properties. (b) All the β 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 β subunits. (d) The modulatory features found here for 1E do not generalize uniformly to other 1 channel types, as 1C activation gating shows marked β 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.
Key Words: calcium channels • 1E • gating currents • subunit modulation • heterologous expression
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