beta 1-Subunit of the Ca2+-activated K+ channel regulates contractile activity of mouse urinary bladder smooth muscle

1. The large-conductance calcium-activated potassium (BK) channel plays an important role in controlling membrane potential and contractility of urina ry bladder smooth muscle (UBSM). These channels are composed of a pore-form ing alpha -subunit and an accessory, smooth muscle-specific, beta1-subunit. 2. Our aim was to determine the functional role of the beta1-subunit of the BK channel in controlling In the contractions of UBSM by using BK channel beta1-subunit 'knock -out' (KO) mice. 3. The beta -galactosidase reporter (lacZ gene) was targeted to the beta1 l ocus, which provided the opportunity to examine the expression of the beta1 -subunit in UBSM Based on this approach, the beta1-subunit is highly expres sed in UBSM. 4. BK channels lacking beta1-subunits have reduced activity, consistent wit h a shift in BK channel voltage/Ca2+ sensitivity. 5. Iberiotoxin, an inhibitor of BK channels, increased the amplitude and de creased the frequency of phasic contractions of UBSM strips from control mi ce. 6. The effects of the beta1-subunit deletion on contractions were similar t o the effect of iberiotoxin on control mice. The UBSM strips from beta1-sub unit KO mice had elevated phasic contraction amplitude and decreased freque ncy when compared to control UBSM strips. 7. Iberiotoxin increased the amplitude and frequency of phasic contractions , and UBSM tone of UBSM strips from beta1-subunit KO mice, suggesting that BK channels still regulate contractions in the absence of the beta1-subunit . 8. The results indicate that the beta1-subunit, by modulating BK channel ac tivity, plays a significant role in the regulation of phasic contractions o f the urinary bladder.