Single channel measurements demonstrate the voltage dependence of permeation through N-type and L-type CaV channels

The delivery of Ca2+ into cells by Ca-V channels provides the trigger for many cellular actions, such as cardiac muscle contraction and neurotransmitter release. Thus, a full understanding of Ca2+ permeation through these channels is critical. Using whole-cell voltage-clamp recordings, we recently demonstrated that voltage modulates the apparent affinity of N-type (Ca(V)2.2) channels for permeating Ca2+ and Ba2+ ions. While we took many steps to ensure the high fidelity of our recordings, problems can occur when Ca-V currents become large and fast, or when currents run down. Thus, we use here single channel recordings to further test the hypothesis that permeating ions interact with N-type channels in a voltage-dependent manner. We also examined L-type (Ca(V)1.2) channels to determine if these channels also exhibit voltage-dependent permeation. Like our whole-cell data, we find that voltage modulates N-channel affinity for Ba2+ at voltages > 0 mV, but has little or no effect at voltages < 0 mV. Furthermore, we demonstrate that permeation through L-channel is also modulated by voltage. Thus, voltage-dependence may be a common feature of divalent cation permeation through Ca(V)1 and Ca(V)2 channels (i.e. high-voltage activated Ca-V channels). The voltage dependence of Ca(V)1 channel permeation is likely a mechanism mediating sustained Ca2+ influx during the plateau phase of the cardiac action potential.