Molecular Origin of the L-Type Ca2+ Current of Skeletal Muscle Myotubes Selectively Deficient in Dihydropyridine Receptor β1a Subunit

Abstract The origin of I βnull , the Ca 2+ current of myotubes from mice lacking the skeletal dihydropyridine receptor (DHPR) β 1a subunit, was investigated. The density of I βnull was similar to that of I dys , the Ca 2+ current of myotubes from dysgenic mice lacking the skeletal DHPR α 1S subunit (−0.6±0.1 and −0.7±0.1 pA/pF, respectively). However, I βnull activated at significantly more positive potentials. The midpoints of the G Ca - V curves were 16.3±1.1mV and 11.7±1.0mV for I βnull and I dys , respectively. I βnull activated significantly more slowly than I dys . At +30mV, the activation time constant for I βnull was 26±3ms, and that for I dys was 7±1ms. The unitary current of normal L-type and β 1 -null Ca 2+ channels estimated from the mean variance relationship at +20mV in 10mM external Ca 2+ was 22±4 fA and 43±7 fA, respectively. Both values were significantly smaller than the single-channel current estimated for dysgenic Ca 2+ channels, which was 84±9 fA under the same conditions. I βnull and I dys have different gating and permeation characteristics, suggesting that the bulk of the DHPR α 1 subunits underlying these currents are different. I βnull is suggested to originate primarily from Ca 2+ channels with a DHPR α 1S subunit. Dysgenic Ca 2+ channels may be a minor component of this current. The expression of DHPR α 1S in β 1 -null myotubes and its absence in dysgenic myotubes was confirmed by immunofluorescence labeling of cells.