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

authors

• Strube Caroline

abstract

The subunit structure of low voltage activated T-type Ca 2+ channels is still unknown. Co-expression of dihydropyridine receptor (DHPR) auxiliary subunits with Ttype α 1 subunits in heterologous systems has produced conflicting results. In developing foetal skeletal muscle fibres which abundantly express DHPR subunits, Ca v 3.2 (α 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 Ca 2+ 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 α 1S (Ca v 1.1), β 1 and γ 1 DHPR subunits was tested using dysgenic (α 1S-null), β 1a and γ 1 knockout mice. The results show that the absence of α 1S , β 1 or γ 1 DHPR subunits does not significantly affect the electrophysiological properties of T-type Ca 2+ currents in skeletal muscle, suggesting that (1) native Ca v 3.2 is not regulated by β 1 or γ 1 DHPR subunits; (2) T-type and L-type currents have distinct and not interchangeable roles. Keywords T-type Ca 2+ channel. Skeletal muscle. β 1 DHPR subunit. γ 1 DHPR subunit. α 1S DHPR subunit. Ca v 3.2. Ca v 1.1

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