Absence of regulation of the T-type calcium current by Cav1.1, β1a and γ1 dihydropyridine receptor subunits in skeletal muscle cells

The subunit structure of low voltage activated T-type Ca2+ channels is still unknown. Co-expression of dihydropyridine receptor (DHPR) auxiliary subunits with T-type alpha(1) subunits in heterologous systems has produced conflicting results. In developing foetal skeletal muscle fibres which abundantly express DHPR subunits, Ca(v)3.2 (alpha(1H)) subunits are believed to underlie T-type calcium currents which disappear 2 to 3 weeks after birth. Therefore, a possible regulation of foetal skeletal muscle T-type Ca2+ channels by DHPR subunits was investigated in freshly isolated foetal skeletal muscle using knockout mice, which provide a powerful tool to address this question. The possible involvement of alpha(1S) (Ca(v)1.1), beta(1) and gamma(1) DHPR subunits was tested using dysgenic (alpha(1S)-null), beta(1a) and gamma(1) knockout mice. The results show that the absence of alpha(1S), beta(1) or gamma(1) DHPR subunits does not significantly affect the electrophysiological properties of T-type Ca2+ currents in skeletal muscle, suggesting that (1) native Ca(v)3.2 is not regulated by beta(1) or gamma(1) DHPR subunits; (2) T-type and L-type currents have distinct and not interchangeable roles.