Facilitation of calcium current by depolarizing prepulses has been observed in man) cells including cardiac muscle, The mechanism underlying prepulse facilitation is controversial with respect to the requirements of channel subunits and cAMP kinase. We found that coexpression of the cardiac alpha(]C-a) subunit with the cardiac beta(2a) subunit significantly promotes the facilitation of I-Ba by strong depolarizing prepulses, The magnitude of I-Ba facilitation depended on the voltage potential of the prepulse and the interval duration beta een prepulse and test pulse. Prepulse facilitation was not affected by coexpression of AKAP79 and conditions favoring cAMP-dependent phosphorylation. Prepulse facilitation was also observed in cells expressing an alpha(1C-a) subunit which was truncated at residue 1733 removing the cAMP kinase site at Ser-1928. Facilitation was abolished by coexpression of the alpha(2)delta-1 or alpha(2)delta-3 subunit, We conclude that the expressed alpha(1C-a) beta(2a) complex is sufficient to support prepulse facilitation. Facilitation is prevented bg coexpression of the alpha(2)delta subunit, (C) 1999 Federation of European Biochemical Societies.