SUBUNIT REGULATION OF THE HUMAN BRAIN ALPHA(1E) CALCIUM-CHANNEL

The alpha(1) subunit coding for the human brain type E calcium channel (Schneider et al., 1994) was expressed in Xenopus oocytes in the abse nce, and in combination with auxiliary alpha(2) delta and beta subunit s. alpha(1E) channels directed with the expression of Ba2+ whole-cell currents that completely inactivated after a 2-sec membrane pulse. Coe xpression of alpha(1E) with alpha(2b)delta shifted the peak current by +10 mV but had no significant effect on whole-cell current inactivati on. Coexpression of alpha(1E) with beta(2a) shifted the peak current r elationship by -10 mV, and strongly reduced Ba2+ current inactivation. This slower rate of inactivation explains that a sizable fraction (40 +/- 10%, n = 8) of the Ba2+ current failed to inactivate completely a fter a 5-sec prepulse. Coinjection with both the cardiac/brain beta(2a ) and the neuronal alpha(2b)delta subunits increased by approximate to 10-fold whole-cell Ba2+ currents although coinjection with either bet a(2a) or alpha(2b)delta alone failed to significantly increase alpha(1 E) peak currents. Coexpression with beta(2a) and alpha(2b)delta yielde d Ba2+ currents with inactivation kinetics similar to the beta(2a) ind uced currents, indicating that the neuronal alpha(2b)delta subunit has little effect on alpha(1E) inactivation kinetics. The subunit specifi city of the changes in current properties were analyzed for all four b eta subunit genes. The slower inactivation was unique to alpha(1E)/bet a(2a) currents. Coexpression with beta(1a), beta(1b), beta(3), and bet a(4), yielded faster-inactivating Ba2+ currents than currents recorded from the or,, subunit alone. Furthermore, alpha(1E)/alpha(2b)delta/be ta(1a); alpha(1E)/alpha(2b)delta/beta(1b); alpha(1E)/alpha(2b)delta/be ta(3); alpha(1E)/alpha(2b)delta/beta(4) channels elicited whole-cell c urrents with steady-state inactivation curves shifted in the hyperpola rized direction. The beta subunit-induced changes in the properties of alpha(1E) channel were comparable to modulation effects reported for alpha(1C) and alpha(1A) channels with beta(3) approximate to beta(1b) > beta(1a) approximate to beta(4) much greater than beta(2a) inducing fastest to slowest rate of whole-cell inactivation.