Distinctive biophysical and pharmacological properties of class A (BI) calcium channel alpha 1 subunits.
Transcripts for the class A Ca2+ channel alpha 1 subunit (also known as BI) are present at high levels in many parts of the mammalian CNS and are widely assumed to encode the P-type Ca2+ channel. To characterize the biophysical and pharmacological properties of alpha 1A channels, macroscopic and single-channel recordings were made in Xenopus oocytes injected with alpha 1A cRNA. alpha 1-specific properties were identified by making systematic comparisons with the more familiar class C alpha 1 subunit under the condition of a standard ancillary subunit (alpha 2/delta + beta) makeup. alpha 1A currents activate and inactivate more rapidly and display steeper voltage dependence of gating than alpha 1C currents. Unlike alpha 1C, alpha 1A channels are largely insensitive to dihydropyridines and FPL 64176, but respond to the cone snail peptide omega-CTx-MVIIC(SNX-230), a potent and fairly selective inhibitor. In comparison with P-type Ca2+ channels in rat cerebellar Purkinje cells, alpha 1A channels in oocytes are approximately 10(2)-fold less sensitive to omega-Aga-IVA and approximately 10-fold more sensitive to omega-CTx-MVIIC. alpha 1A channels are not inhibited by Bay K 8644 and inactivate much more rapidly than P-type Ca2+ channels. Thus, alpha 1A is capable of generating a Ca2+ channel phenotype quite different from P-type current.
Sather
W A
WA
Department of Molecular and Cellular Physiology, Stanford University, California 94305-5426.
Tanabe
T
T
Zhang
J F
JF
Mori
Y
Y
Adams
M E
ME
Tsien
R W
RW
D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology; D004594:Electrophysiology / Q000379:methods; D007700:Kinetics; D008978:Mollusk Venoms / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D013111:Spider Venoms / Q000494:pharmacology; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D008978:Mollusk Venoms; D010455:Peptides; D011758:Pyrroles; D013111:Spider Venoms; D020960:omega-Conotoxins; D002104:Cadmium; C071658:FPL 64176; C075851:omega-conotoxin-MVIIC