The α(1E) calcium channel exhibits permeation properties similar to low-voltage-activated calcium channels

Abstract

The physiological and pharmacological properties of the α(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, β 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 α(1E) closely resemble those described for a subset of low-threshold Ca channels. The α(1A) (P-/Q-type), α(1B) (N-type), and α(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 α(1E) currents are largest in Sr, followed by Ca and then Ba. The unique permeation properties of α(1E) are maintained at the single-channel level, are independent of the nature of the expression system, and are not affected by coexpression of α2 and β subunits. Overall, the permeation characteristics of α(1E) are distinct from those described for R-type currents and share some similarities with native low-threshold Ca channels.