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.