Role of extracellular Ca 2+ in gating of Ca V 1.2 channels

We examined changes in ionic and gating currents in Ca V 1.2 channels when extracellular Ca 2+ was reduced from 10 m m to 0.1 μ m . Saturating gating currents decreased by two‐thirds ( K D ≈ 40 μ m ) and ionic currents increased 5‐fold ( K D ≈ 0.5 μ m ) due to increasing Na + conductance. A biphasic time dependence for the activation of ionic currents was observed at low [Ca 2+ ], which appeared to reflect the rapid activation of channels that were not blocked by Ca 2+ and a slower reversal of Ca 2+ blockade of the remaining channels. Removal of Ca 2+ following inactivation of Ca 2+ currents showed that Na + currents were not affected by Ca 2+ ‐dependent inactivation. Ca 2+ ‐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 Ca 2+ conductance and Ca 2+ ‐dependent inactivation depend on extracellular Ca 2+ and are linked to changes in selectivity.