Abstract:
:Voltage-dependent G-protein inhibition of N-type calcium channels reduces presynaptic calcium entry, sharply attenuating neurotransmitter release. Studies in neurons demonstrate that G-proteins have multiple modulatory effects on N-type channels. The observed changes may reflect genuine complexity in G-protein action and/or the intricate interactions of multiple channels and receptors in neurons. Expression of recombinant M2-muscarinic receptors and N-type channels in HEK 293 cells allowed voltage-dependent inhibition to be studied in isolation. In this system, receptor-activated G-proteins had only one effect: a 10-fold increase in the time required for channels to first open following membrane depolarization. There were no changes in gating after the channel first opened, and unitary currents were not detectably altered by modulation. Despite its simplicity, this single change successfully accounts for the complex alterations in whole-cell current observed during G-protein inhibition in neurons.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Patil PG,de Leon M,Reed RR,Dubel S,Snutch TP,Yue DTdoi
10.1016/S0006-3495(96)79444-4subject
Has Abstractpub_date
1996-11-01 00:00:00pages
2509-21issue
5eissn
0006-3495issn
1542-0086pii
S0006-3495(96)79444-4journal_volume
71pub_type
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