Structural determinants for functional coupling between the ? and ? subunits in the Ca2+-activated K+ (BK) channel

Orio, P; Torres Y.; Rojas P.; Carvacho I.; Latorre R.; Garcia, M. L.; Toro, L.; Valverde M.A.

Keywords: sequence, membrane, tertiary, animals, expression, potentials, protein, cell, gene, clamp, structure, channel, subunits, chain, calcium, alpha, beta, laevis, humans, potassium, patch-clamp, subunit, xenopus, electrophysiology, oocytes, female, drug, article, large-conductance, myometrium, function, oocyte, techniques, controlled, chimera, animal, study, nucleotide, relationship, amino, nonhuman, Structure-Activity, patch, unclassified, activated, Structure,, carboxy, terminal, Channels,, Calcium-Activated, Voltage-Gated


High conductance, calcium- and voltage-activated potassium (BK, MaxiK) channels are widely expressed in mammals. In some tissues, the biophysical properties of BK channels are highly affected by coexpression of regulatory (?) subunits. The most remarkable effects of ?1 and ?2 subunits are an increase of the calcium sensitivity and the slow down of channel kinetics. However, the detailed characteristics of channels formed by ? and ?1 or ?2 are dissimilar, the most remarkable difference being a reduction of the voltage sensitivity in the presence of ?1 but not ?2. Here we reveal the molecular regions in these ? subunits that determine their differential functional coupling with the pore-forming ?-subunit. We made chimeric constructs between ?1 and ?2 subunits, and BK channels formed by ? and chimeric ? subunits were expressed in Xenopus laevis oocytes. The electrophysiological characteristics of the resulting channels were determined using the patch clamp technique. Chimeric exchange of the different regions of the ?1 and ?2 subunits demonstrates that the NH3 and COOH termini are the most relevant regions in defining the behavior of either subunit. This strongly suggests that the intracellular domains are crucial for the fine tuning of the effects of these ? subunits. Moreover, the intracellular domains of ?1 are responsible for the reduction of the BK channel voltage dependence. This agrees with previous studies that suggested the intracellular regions of the ?-subunit to be the target of the modulation by the ?1-subunit. © The Rockefeller University Press.

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Volumen: 127
Número: 2
Fecha de publicación: 2006
Página de inicio: 191
Página final: 204