Stimulation of β3-adrenoceptors relaxes rat urinary bladder smooth muscle via activation of the large-conductance Ca²⁺-activated K⁺ channels

Sep 19, 2008American journal of physiology. Cell physiology

Activating beta3-adrenoceptors relaxes rat bladder muscle by opening large calcium-activated potassium channels

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Abstract

BRL 37344 increased spontaneous, transient outward BK current frequency by 46.0% in rat urinary bladder smooth muscle.

Stimulation of beta3-adrenoceptors may inhibit spontaneous contractions in urinary bladder smooth muscle strips.
The effect of BRL 37344 is reduced by both a beta3-AR antagonist and a PKA inhibitor.
Inhibition of BK channels shifts the response curves for muscle contraction to the right, indicating reduced relaxation.
BRL 37344 causes hyperpolarization of the membrane potential from -26.1 mV to -29.0 mV.
The increase in BK channel current frequency may contribute to the relaxation of the bladder smooth muscle.

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We investigated the role of large-conductance Ca(2+)-activated K(+) (BK) channels in beta3-adrenoceptor (beta3-AR)-induced relaxation in rat urinary bladder smooth muscle (UBSM). BRL 37344, a specific beta3-AR agonist, inhibits spontaneous contractions of isolated UBSM strips. SR59230A, a specific beta3-AR antagonist, and H89, a PKA inhibitor, reduced the inhibitory effect of BRL 37344. Iberiotoxin, a specific BK channel inhibitor, shifts the BRL 37344 concentration response curves for contraction amplitude, net muscle force, and tone to the right. Freshly dispersed UBSM cells and the perforated mode of the patch-clamp technique were used to determine further the role of beta3-AR stimulation by BRL 37344 on BK channel activity. BRL 37344 increased spontaneous, transient, outward BK current (STOC) frequency by 46.0 +/- 20.1%. In whole cell mode at a holding potential of V(h) = 0 mV, the single BK channel amplitude was 5.17 +/- 0.28 pA, whereas in the presence of BRL 37344, it was 5.55 +/- 0.41 pA. The BK channel open probability was also unchanged. In the presence of ryanodine and nifedipine, the current-voltage relationship in response to depolarization steps in the presence and absence of BRL 37344 was identical. In current-clamp mode, BRL 37344 caused membrane potential hyperpolarization from -26.1 +/- 2.1 mV (control) to -29.0 +/- 2.2 mV. The BRL 37344-induced hyperpolarization was eliminated by application of iberiotoxin, tetraethylammonium or ryanodine. The data indicate that stimulation of beta3-AR relaxes rat UBSM by increasing the BK channel STOC frequency, which causes membrane hyperpolarization and thus relaxation.

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Stimulation of β3-adrenoceptors relaxes rat urinary bladder smooth muscle via activation of the large-conductance Ca²⁺-activated K⁺ channels

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