Biophys J, July 2001, p. 89-96, Vol. 81, No. 1

Ca²⁺ Channel Inactivation Heterogeneity Reveals Physiological Unbinding of Auxiliary  Subunits

CRBM, CNRS UPR 1086, UFR 24, 34293 Montpellier Cedex 05, France

Voltage gated Ca²⁺ channel (VGCC) auxiliary  subunits increase membrane expression of the main pore-forming ₁ subunits and finely tune channel activation and inactivation properties. In expression studies, co-expression of  subunits also reduced neuronal Ca²⁺ channel regulation by heterotrimeric G protein. Biochemical studies suggest that VGCC  subunits and G protein can compete for overlapping interaction sites on VGCC ₁ subunits, suggesting a dynamic association of these subunits with ₁. In this work we have analyzed the stability of the ₁/ association under physiological conditions. Regulation of the _1A Ca²⁺ channel inactivation properties by _1b and _2a subunits had two major effects: a shift in voltage-dependent inactivation (E_in), and an increase of the non-inactivating current (R_in). Unexpectedly, large variations in magnitude of the effects were recorded on E_in, when _1b was expressed, and R_in, when _2a was expressed. These variations were not proportional to the current amplitude, and occurred at similar levels of  subunit expression. _2a-induced variations of R_in were, however, inversely proportional to the magnitude of G protein block. These data underline the two different mechanisms used by _1b and _2a to regulate channel inactivation, and suggest that the VGCC  subunit can unbind the 1 subunit in physiological situations.

Biophys J, July 2001, p. 89-96, Vol. 81, No. 1
© 2001 by the Biophysical Society   0006-3495/01/07/89/08  $2.00

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