RT Journal Article SR Electronic T1 Ca2+/Calmodulin-Dependent Facilitation and Inactivation of P/Q-Type Ca2+ Channels JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 6830 OP 6838 DO 10.1523/JNEUROSCI.20-18-06830.2000 VO 20 IS 18 A1 Amy Lee A1 Todd Scheuer A1 William A. Catterall YR 2000 UL http://www.jneurosci.org/content/20/18/6830.abstract AB Trains of action potentials cause Ca2+-dependent facilitation and inactivation of presynaptic P/Q-type Ca2+ channels that can alter synaptic efficacy. A potential mechanism for these effects involves calmodulin, which associates in a Ca2+-dependent manner with the pore-forming α1A subunit. Here, we report that Ca2+ and calmodulin dramatically enhance inactivation and facilitation of P/Q-type Ca2+channels containing the auxiliary β2a subunit compared with their relatively small effects on channels with β1b. Tetanic stimulation causes an initial enhancement followed by a gradual decline in P/Q-type Ca2+ currents over time. Recovery of Ca2+ currents from facilitation and inactivation is relatively slow (30 sec to 1 min). These effects are strongly inhibited by high intracellular BAPTA, replacement of extracellular Ca2+ with Ba2+, and a calmodulin inhibitor peptide. The Ca2+/calmodulin-dependent facilitation and inactivation of P/Q-type Ca2+ channels observed here are consistent with the behavior of presynaptic Ca2+ channels in neurons, revealing how dual feedback regulation of P/Q-type channels by Ca2+ and calmodulin could contribute to activity-dependent synaptic plasticity.