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This Article Full Text Full Text (PDF) Supplementary Material All Versions of this Article: 553/2/473    most recent jphysiol.2003.051110v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, Z. Articles by Murphy, T. H. Search for Related Content PubMed PubMed Citation Articles by Liu, Z. Articles by Murphy, T. H.

Decoding of synaptic voltage waveforms by specific classes of recombinant high-threshold Ca²⁺ channels

Zhi Liu*§, Jihong Ren*§ and Timothy H. Murphy*†‡§

Studies suggest that the preferential role of L-type voltage-sensitive Ca²⁺ channels (VSCCs) in coupling strong synaptic stimulation to transcription is due to their selective activation of local chemical events. However, it is possible that selective activation of the L-type channel by specific voltage waveforms also makes a contribution. To address this issue we have examined the response of specific Ca²⁺ channel types to simulated complex voltage waveforms resembling those encountered during synaptic plasticity (gamma and theta firing frequency). L-, P/Q- and N-type VSCCs (_1C, _1A, _1B/_1B/₂, respectively) were all similarly activated by brief action potential (AP) waveforms or sustained step depolarization. When complex waveforms containing large excitatory postsynaptic potentials (EPSPs), APs and spike accommodation were applied under voltage clamp we found that the integrated L-type VSCC current was approximately three times larger than that produced by the P/Q- or N-type Ca²⁺ channels (gamma frequency 1 s stimulation). For P/Q- or N-type channels the complex waveforms led to a smaller current than that expected from the response to a simple 1 s step depolarization to 0 or +20 mV. EPSPs present in the waveforms favoured the inactivation of P/Q- and N-type channels. In contrast, activation of the L-type channel was dependent on both EPSP- and AP-mediated depolarization. Expression of P/Q-type channels with reduced voltage-dependent inactivation (_1A/_2A/₂) or the use of hyperpolarized intervals between AP stimuli greatly increased their response to complex voltage stimuli. We propose that in response to complex synaptic voltage waveforms P/Q- and N-type channels can undergo selective voltage-dependent inactivation leading to a Ca²⁺ current mediated predominantly by L-type channels.

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