The novel beta3 accessory subunit confers rapid inactivation on BK channels when coexpressed with the Slo alpha-subunit, explaining the inactivating phenotype of native BK channels in chromaffin and RIN cells.
The beta3 accessory subunit confers rapid inactivation and reduced charybdotoxin sensitivity to BK channels, explaining the native inactivating phenotype seen in adrenal chromaffin and RIN cells.
Large-conductance Ca2+- and voltage-dependent potassium (BK) channels exhibit functional diversity not explained by known splice variants of the single Slo alpha-subunit. Here we describe an accessory subunit (beta3) with homology to other beta-subunits of BK channels that confers inactivation when it is coexpressed with Slo. Message encoding the beta3 subunit is found in rat insulinoma tumor (RINm5f) cells and adrenal chromaffin cells, both of which express inactivating BK channels. Channels resulting from coexpression of Slo alpha and beta3 subunits exhibit properties characteristic of native inactivating BK channels. Inactivation involves multiple cytosolic, trypsin-sensitive domains. The time constant of inactivation reaches a limiting value approximately 25-30 msec at Ca2+ of 10 microM and positive activation potentials. Unlike Shaker N-terminal inactivation, but like native inactivating BK channels, a cytosolic channel blocker does not compete with the native inactivation process. Finally, the beta3 subunit confers a reduced sensitivity to charybdotoxin, as seen with native inactivating BK channels. Inactivation arises from the N terminal of the beta3 subunit. Removal of the beta3 N terminal (33 amino acids) abolishes inactivation, whereas the addition of the beta3 N terminal onto the beta1 subunit confers inactivation. The beta3 subunit shares with the beta1 subunit an ability to shift the range of voltages over which channels are activated at a given Ca2+. Thus, the beta-subunit family of BK channels regulates a number of critical aspects of BK channel phenotype, including inactivation and apparent Ca2+ sensitivity.
Xia et al. (1999) studied this question. beta3 subunit coexpression vs. Slo alpha-subunit alone was evaluated on Channel inactivation properties. The novel beta3 accessory subunit confers rapid inactivation on BK channels when coexpressed with the Slo alpha-subunit, explaining the inactivating phenotype of native BK channels in chromaffin and RIN cells.