Key result
Reducing extracellular Ca2+ from 10 mM to 0.1 µM decreased saturating gating currents by two-thirds and increased ionic currents 5-fold due to increasing Na+ conductance in CaV1.2 channels.
Extracellular Ca2+ levels regulate the activation of Ca2+ conductance and Ca2+-dependent inactivation in CaV1.2 channels, linking them to changes in channel selectivity.
Extends CaV1.2 channel biophysics in animal models; leaves open relevance to human cardiac electrophysiology or therapy.
We examined changes in ionic and gating currents in Ca(V)1.2 channels when extracellular Ca(2+) was reduced from 10 mm to 0.1 microm. Saturating gating currents decreased by two-thirds (K(D) approximately 40 microm) and ionic currents increased 5-fold (K(D) approximately 0.5 microm) 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.
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Babich et al. (2005) studied this question. Reduction of extracellular Ca2+ vs. 10 mm extracellular Ca2+ was evaluated on Changes in ionic and gating currents in Ca(V)1.2 channels. Reducing extracellular Ca2+ from 10 mM to 0.1 µM decreased saturating gating currents by two-thirds and increased ionic currents 5-fold due to increasing Na+ conductance in CaV1.2 channels.
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