The class A Ca2+ channel alpha 1 subunit (alpha 1A) was expressed in Xenopus oocytes alone or in combination with the beta 1b, beta 2a, beta 3, or beta 4 subunit. Analysis of voltage-dependent activation and inactivation in the presence of 1.8 mM external Ca2+ showed an hyperpolarising shift of both relations when compared to similar recordings performed in the presence of 40 mM Ba2+. These shifts, which differed for activation and inactivation, were strongly modulated by the nature of the coexpressed beta subunit. On the other hand, for each combination, the kinetics of inactivation were similar in 1.8 mM Ca2+ and 40 mM Ba2+ (for example co-expression of the beta 2a subunit reduced inactivation using either 40 mM Ba2+ or 1.8 mM Ca2+). Thus, modulation of channel properties by the beta subunit is different in physiological Ca2+ or high Ba2+ concentrations. These results must be taken into consideration to extrapolate the role of the beta subunit in native cells.