The α_1ECalcium Channel Exhibits Permeation Properties Similar to Low-Voltage-Activated Calcium Channels

Abstract

The physiological and pharmacological properties of the ␣ 1E calcium (Ca) channel subtype do not exactly match any of the established categories described for native neuronal Ca currents. Many of the key diagnostic features used to assign cloned Ca channels to their native counterparts, however, are dependent on a number of factors, including cellular environment, ␤ subunit coexpression, and modulation by second messengers and G-proteins. Here, by examining the intrinsic pore characteristics of a family of transiently expressed neuronal Ca channels, we demonstrate that the permeation properties of ␣ 1E closely resemble those described for a subset of lowthreshold Ca channels. The ␣ 1A (P-/Q-type), ␣ 1B (N-type), and ␣ 1C (L-type) high-threshold Ca channels all exhibit larger whole-cell currents with barium (Ba) as the charge carrier as compared with Ca or strontium (Sr). In contrast, macroscopic ␣ 1E currents are largest in Sr, followed by Ca and then Ba. The unique permeation properties of ␣ 1E are maintained at the single-channel level, are independent of the nature of the expression system, and are not affected by coexpression of ␣ 2 and ␤ subunits. Overall, the permeation characteristics of ␣ 1E are distinct from those described for R-type currents and share some similarities with native low-threshold Ca channels.

Differences in Apparent Pore Sizes of Low and High Voltage-activated Ca2+ Channels

“…they show little discrimination among divalent cations) or at least equal in size (because Ca V 2.3 is highly homologous to other HVA ␣ 1 subunits). Once again, our observations of a smaller cutoff size for organic cation permeation through R-type channels ran counter to what might have been expected a priori, although they do reinforce previous evidence that R-type channels differ significantly from other HVA channels in their selectivity properties but share some characteristics of T-type channels (39).…”

“…Ca V 1.2 (␣ 1C ), the subject of the vast majority of recent permeation experiments, was a logical starting point for comparison with the three T-type channel subunits, Ca V 3.1, Ca V 3.2, and Ca V 3.3. We also studied the pore size of channels encoded by the Ca V 2.3 subunit (␣ 1E ), which supports the R-type current (38), of interest because this channel resembles T-type channels in permeation and selectivity properties, although its amino acid sequence is much closer to L-than T-type ␣ 1 subunits (39,40).…”

T‐type Ca2+ channels and α1E expression in spermatogenic cells, and their possible relevance to the sperm acrosome reaction

“…This channel shows transient kinetics when expressed in Xenopus oocytes, and is sensitive to external Ni 2+ (ICs0 = 28 gM). As the low-threshold Ca 2+ channels, ale is able to transport Ca 2+ only slightly more efficiently than Ba 2+ [35]. This is also the case for the spermatogenic cell expressed Ca 2+ channels, both in rat [30] and in the mouse [33].…”

“…Heterologous expression of several structurally related members of the ale has shown a large variation in the voltage-dependence of channel activation [35][36][37][38]. The biophysical properties of heterologously expressed eq subunits depend on the auxiliary subunits coexpressed, particularly the 13 sub- units [39].…”

Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels

“…For example, the L-type channel conductance drops threefold in Ca 2ϩ (149,367). Recombinant Ca v 2.1 and Ca v 2.2 channels also preferentially conduct Ba 2ϩ (Ͼ2-fold), whereas Ca v 2.3 conducts both ions equally well (56). In contrast, native T-type channels conduct Ca 2ϩ and Ba 2ϩ (and Sr 2ϩ ) equally well (64,104,367,368).…”