Differential gating and recruitment of P/Q-, N-, and R-type Ca(2+) channels in hippocampal mossy fiber boutons Journal Article

Author(s): Li, Liyi; Bischofberger, Josef; Jonas, Peter
Article Title: Differential gating and recruitment of P/Q-, N-, and R-type Ca(2+) channels in hippocampal mossy fiber boutons
Abstract: Voltage-gated Ca2+ channels in presynaptic terminals initiate the Ca2+ inflow necessary for transmitter release. At a variety of synapses, multiple Ca2+ channel subtypes are involved in synaptic transmission and plasticity. However, it is unknown whether presynaptic Ca2+ channels differ in gating properties and whether they are differentially activated by action potentials or subthreshold voltage signals. We examined Ca2+ channels in hippocampal mossy fiber boutons (MFBs) by presynaptic recording, using the selective blockers omega-agatoxin IVa, omega-conotoxin GVIa, and SNX-482 to separate P/Q-, N-, and R-type components. Nonstationary fluctuation analysis combined with blocker application revealed a single MFB contained on average approximately 2000 channels, with 66% P/Q-, 26% N-, and 8% R-type channels. Whereas both P/Q-type and N-type Ca2+ channels showed high activation threshold and rapid activation and deactivation, R-type Ca2+ channels had a lower activation threshold and slower gating kinetics. To determine the efficacy of activation of different Ca2+ channel subtypes by physiologically relevant voltage waveforms, a six-state gating model reproducing the experimental observations was developed. Action potentials activated P/Q-type Ca2+ channels with high efficacy, whereas N- and R-type channels were activated less efficiently. Action potential broadening selectively recruited N- and R-type channels, leading to an equalization of the efficacy of channel activation. In contrast, subthreshold presynaptic events activated R-type channels more efficiently than P/Q- or N-type channels. In conclusion, single MFBs coexpress multiple types of Ca2+ channels, which are activated differentially by subthreshold and suprathreshold presynaptic voltage signals.
Keywords: Animals; Rats; Rats, Wistar; Synaptic Transmission/physiology; Calcium Channels/physiology; Calcium Channels, N-Type/physiology; Calcium Channels, P-Type/*physiology; Electric Stimulation/methods; Presynaptic Terminals/physiology; Ion Channel Gating/physiology; Mossy Fibers, Hippocampal/physiology; Calcium Channels, R-Type/physiology; Recruitment, Neurophysiological/physiology
Journal Title: Journal of Neuroscience
Volume: 27
Issue 49
ISSN: 1529-2401
Publisher: Society for Neuroscience  
Publication Place: United States
Date Published: 2007-01-01
Start Page: 13420
End Page: 9
DOI: 10.1523/JNEUROSCI.1709-07.2007
Open access: no