Permeation of monovalent cations through the non-capacitative arachidonate-regulated Ca2+ Channels in HEK293 cells -: Comparison with endogenous store-operated channels

In a manner similar to voltage-gated Ca2+ channels and Ca2+ release-activated Ca2+ (CRAC) channels, the recently identified arachidonate-regulated Ca2+ (ARC) channels display a large monovalent conductance upon removal of external divalent cations. Using whole-cell patch-clamp recording, we have characterized the properties of these monovalent currents in HEK293 cells stably transfected with the m3 muscarinic receptor and compared them with the corresponding currents through the endogenous store-operated Ca2+ (SOC) channels in the same cells. Although the monovalent currents seen through these two channels displayed certain similarities, several marked differences were also apparent, including the magnitude of the monovalent current/Ca2+ current ratio, the rate and nature of the spontaneous decline in the currents, and the effects of external monovalent cation substitutions and removal of internal Mg2+. Moreover, monovalent ARC currents could be activated after the complete spontaneous inactivation of the corresponding SOC current :in the same cell. We conclude that the non-capacitative ARC channels share, with voltage-gated Ca2+ channels and store-operated Ca2+ channels (e.g, SOC and CRAC the general property of monovalent ion permeation in the nominal absence of extracellular divalent ions. However, the clear differences between the properties of these currents through ARC and SOC channels in the same cell confirm that these represent distinct conductances.