Role of extracellular Ca2+ in gating of CaV1.2 channels

摘要

We examined changes in ionic and gating currents in CaV1.2 channels when extracellular Ca²⁺ was reduced from 10 mm to 0.1 μm. Saturating gating currents decreased by two-thirds (KD≈ 40 μm) and ionic currents increased 5-fold (KD≈ 0.5 μm) due to increasing Na⁺ conductance. A biphasic time dependence for the activation of ionic currents was observed at low [Ca²⁺], which appeared to reflect the rapid activation of channels that were not blocked by Ca²⁺ and a slower reversal of Ca²⁺ blockade of the remaining channels. Removal of Ca²⁺ following inactivation of Ca²⁺ currents showed that Na⁺ currents were not affected by Ca²⁺-dependent inactivation. Ca²⁺-dependent inactivation also induced a negative shift of the reversal potential for ionic currents suggesting that inactivation alters channel selectivity. Our findings suggest that activation of Ca²⁺ conductance and Ca²⁺-dependent inactivation depend on extracellular Ca²⁺ and are linked to changes in selectivity.