DISTINCTIVE BIOPHYSICAL AND PHARMACOLOGICAL PROPERTIES OF CLASS-A (BI) CALCIUM-CHANNEL ALPHA(1)-SUBUNITS

Transcripts for the class A Ca2+ channel alpha1 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 alpha1A channels, macroscopic and single-channel recordings were made in Xenopus oocytes injected with alpha1A cRNA. Alpha1-specific properties were identified by making systematic comparisons with the more familiar class C alpha1 subunit under the condition of a standard ancillary subunit (alpha2/delta + beta) makeup. alpha1A currents activate and inactivate more rapidly and display steeper voltage dependence of gating than alpha1C currents. Unlike alpha1C, alpha1A 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, alpha1A channels in oocytes are approximately 10(2)-fold less sensitive to omega-Aga-IVA and approximately 10-fold more sensitive to omega-CTx-MVIIC. Alpha1A channels are not inhibited by Bay K 8644 and inactivate much more rapidly than P-type Ca2+ channels. Thus, alpha1A is capable of generating a Ca2+ channel phenotype quite different from P-type current.