Abstract
Large-conductance Ca2+-activated (BK) channels, expressed in a variety of tissues, play a fundamental role in regulating and maintaining arterial tone. We recently demonstrated that the slow voltage indicator DiBAC4(3) does not depend, as initially proposed, on the β1 or β4 subunits to activate native arterial smooth muscle BK channels. Using recombinant mslo BK channels, we now show that the β1 subunit is not essential to this activation but exerts a large potentiating effect. DiBAC4(3) promotes concentration-dependent activation of BK channels and slows deactivation kinetics, changes that are independent of Ca2+. Kd values for BK channel activation by DiBAC4(3) in 0 mM Ca2+ are approximately 20 μM (α) and 5 μM (α+β1), and G-V curves shift up to −40mV and −110 mV, respectively. β1 to β2 mutations R11A and C18E do not interfere with the potentiating effect of the subunit. Our findings should help refine the role of the β1 subunit in cardiovascular pharmacology.
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