Voltage-dependent facilitation of a neuronal alpha 1C L-type calcium channel.
Calcium entry into excitable cells through voltage-gated calcium channels can be influenced by both the rate and pattern of action potentials. We report here that a cloned neuronal alpha 1C L-type calcium channel can be facilitated by positive pre-depolarization. Both calcium and barium were effective as charge carriers in eliciting voltage-dependent facilitation. The induction of facilitation was shown to be independent of intracellular calcium levels, G-protein interaction and the level of phosphatase activity. Facilitation was reduced by the injection of inhibitors of protein kinase A and required the coexpression of a calcium channel beta subunit. In contrast, three neuronal non-L-type calcium channels, alpha 1A, alpha 1B and alpha 1E, were not subject to voltage-dependent facilitation when coexpressed with a beta subunit. The results indicate that the mechanism of neuronal L-type calcium channel facilitation involves the interaction of alpha 1 and beta subunits and is dependent on protein kinase A activity. The selective voltage-dependent modulation of L-type calcium channels is likely to play an important role in neuronal physiology and plasticity.
Biotechnology Laboratory, University of British Columbia, Vancouver, Canada.
E
E
Bourinet
P
P
Charnet
W J
WJ
Tomlinson
A
A
Stea
T P
TP
Snutch
J
J
Nargeot
D000818:Animals; D001923:Brain Chemistry; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000145:classification* / Q000235:genetics / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015640:Ion Channel Gating / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology*; D009474:Neurons / Q000737:chemistry; D009865:Oocytes; D011487:Protein Conformation; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D014981:Xenopus
D015220:Calcium Channels; D011994:Recombinant Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium