Stephens, GJ and Page, KM and Bogdanov, Y and Dolphin, AC (2000) The alpha 1B Ca2+ channel amino terminus contributes determinants for beta subunit-mediated voltage-dependent inactivation properties. J PHYSIOL-LONDON , 525 (2) 377 - 390.
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1. Co-expression of auxiliary beta subunits with the alpha 1 beta Ca2+ channel subunit in COS-7 cells resulted in an increase in current density and a hyperpolarising shift in the mid-point of activation. Amongst the beta subunits, beta 2a in particular, but also beta 4 and beta 1b caused a significant retardation of the voltage-dependent inactivation compared to currents with alpha 1B alone, whilst no significant changes in inactivation properties were seen for the beta 3 subunit in this system.2. Prevention of beta 2a palmitoylation, by introducing cysteine to serine mutations (beta 2a(C3,4S)), greatly reduced the ability of beta 2a to retard voltage-dependent inactivation.3. Deletion of the proximal half of the alpha 1B cytoplasmic amino terminus (alpha 1B(Delta 1-55)) differentially affected beta subunit-mediated voltage-dependent inactivation properties. These effects were prominent with the beta 2a subunit and, to a lesser extent, with beta 1b. For beta 2a, the major effects of this deletion were a partial reversal of beta 2a-mediated retardation of inactivation and the introduction of a fast component of inactivation, not seen with full-length alpha 1B. Deletion of the amino terminus had no other major effects on the measured biophysical properties of alpha 1B when co-expressed with beta subunits.4. Transfer of the whole alpha 1B amino terminus into alpha 1C (alpha 1bCCCC) conferred a similar retardation of inactivation on alpha 1C when co-expressed with beta 2a to that seen in parental alpha 1B.5. Individual (alpha 1B(Q47A) and alpha 1B(R52A)) and double (alpha 1B(R52,54A)) point mutations within the amino terminus of alpha 1B also opposed the beta 2a-mediated retardation of alpha 1B inactivation kinetics.6. These results indicate that the alpha 1B amino terminus contains determinants for beta subunit-mediated voltage-dependent inactivation properties. Furthermore, effects were beta subunit selective. As deletion of the alpha 1B amino terminus only partially opposed beta subunit-mediated changes in inactivation properties, the amino terminus is likely to contribute to a complex site necessary for complete beta subunit function.
|Title:||The alpha 1B Ca2+ channel amino terminus contributes determinants for beta subunit-mediated voltage-dependent inactivation properties|
|Keywords:||ALPHA(1E) CALCIUM CHANNELS, G-PROTEIN MODULATION, MOLECULAR DETERMINANTS, CHARGE MOVEMENT, IONIC CURRENT, GAMMA, IDENTIFICATION, PALMITOYLATION, EXPRESSION, INHIBITION|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Neuroscience, Physiology and Pharmacology|
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