A BETA-SUBUNIT NORMALIZES THE ELECTROPHYSIOLOGICAL PROPERTIES OF A CLONED N-TYPE CA2+ CHANNEL ALPHA(1)-SUBUNIT

The electrophysiological and pharmacological properties of a cloned rat brain N-type Ca2+ channel were determined by transient expression in Xenopus oocytes. Expression of the class B Ca2+ channel alpha1 subunit, rbB-I, resulted in a high voltage-threshold current that activated slowly and showed little inactivation over 800 msec. Characteristic of N-type currents, the rbB-I current was completely blocked by omega-conotoxin GVIA and was insensitive to nifedipine and Bay K8644. The modulatory effects on the rbB-I current by cloned rat brain Ca2+ channel alpha2 and beta1b subunits were also examined. Coexpression of rbB-I with the beta1b subunit caused significant changes in the properties of the rbB-I current making it more similar to N-type currents in neurons. These included: (1) an increase in the whole-cell current, (2) an increased rate of activation, (3) a shift of the voltage-dependence of inactivation to hyperpolarized potentials and (4) a pronounced inactivation of the current over 800 msec. Coexpression with the rat brain alpha2 subunit had no significant effect on the rbB-I current alone but appeared to potentiate the rbB-I + beta1b whole cell current. The results show that coexpression with the brain beta1b subunit normalizes the rbB-I N-type current, and suggests the possibility that differences in subunit composition may contribute to the heterogeneous properties described for N-type channels in neurons.