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首页> 外文期刊>American Journal of Physiology >Differential regulation of Ca2+-activated K+ channels by beta-adrenoceptors in guinea pig urinary bladder smooth muscle.
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Differential regulation of Ca2+-activated K+ channels by beta-adrenoceptors in guinea pig urinary bladder smooth muscle.

机译：β-肾上腺素受体在豚鼠膀胱平滑肌中对Ca2 +激活的K +通道的差异调节。

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Stimulation of beta-adrenoceptors contributes to the relaxation of urinary bladder smooth muscle (UBSM) through activation of large-conductance Ca(2+)-activated K(+) (BK) channels. We examined the mechanisms by which beta-adrenoceptor stimulation leads to an elevation of the activity of BK channels in UBSM. Depolarization from -70 to +10 mV evokes an inward L-type dihydropyridine-sensitive voltage-dependent Ca(2+) channel (VDCC) current, followed by outward steady-state and transient BK current. In the presence of ryanodine, which blocks the transient BK currents, isoproterenol, a nonselective beta-adrenoceptor agonist, increased the VDCC current by approximately 25% and the steady-state BK current by approximately 30%. In the presence of the BK channel inhibitor iberiotoxin, isoproterenol did not cause activation of the remaining steady-state K(+) current component. Decreasing Ca(2+) influx through VDCC by nifedipine or depolarization to +80 mV suppressed the isoproterenol-induced activation of the steady-state BK current. Unlike forskolin, isoproterenol did not change significantly the open probability of single BK channels in the absence of Ca(2+) sparks and with VDCC inhibited by nifedipine. Isoproterenol elevated Ca(2+) spark (local intracellular Ca(2+) release through ryanodine receptors of the sarcoplasmic reticulum) frequency and associated transient BK currents by approximately 1.4-fold. The data support the concept that in UBSM beta-adrenoceptor stimulation activates BK channels by elevating Ca(2+) influx through VDCC and by increasing Ca(2+) sparks, but not through a Ca(2+)-independent mechanism. This study reveals key regulatory molecular and cellular mechanisms of beta-adrenergic regulation of BK channels in UBSM that could provide new targets for drugs in the treatment of bladder dysfunction.
机译：β肾上腺素受体的刺激通过激活大电导Ca（2+）激活的K（+）（BK）通道，有助于松弛膀胱平滑肌（UBSM）。我们检查了β-肾上腺素受体刺激导致UBSM中BK通道活性升高的机制。从-70到+10 mV的去极化会引起向内L型二氢吡啶敏感的电压依赖性Ca（2+）通道（VDCC）电流，接着是向外的稳态和瞬态BK电流。在能阻止瞬态BK电流的ryanodine存在下，异丙肾上腺素（一种非选择性β-肾上腺素受体激动剂）可使VDCC电流增加约25％，使稳态BK电流增加约30％。在BK通道抑制剂iberiotoxin的存在下，异丙肾上腺素不会引起剩余的稳态K（+）电流组件的激活。减少通过硝苯地平通过VDCC的Ca（2+）流入或去极化至+80 mV，抑制了异丙肾上腺素诱导的稳态BK电流的激活。与佛司可林不同，异丙肾上腺素在没有Ca（2+）火花和硝苯地平抑制VDCC的情况下，不会显着改变单个BK通道的打开概率。异丙肾上腺素升高Ca（2+）火花（通过肌浆网的ryanodine受体释放局部细胞内Ca（2+））频率和相关的瞬时BK电流约1.4倍。数据支持的概念是，UBSMβ-肾上腺素能受体刺激通过升高VDCC的Ca（2+）流入量和通过增加Ca（2+）火花而不是通过Ca（2+）独立机制来激活BK通道。这项研究揭示了UBSM中BK通道的β-肾上腺素调节的关键调节分子和细胞机制，可以为治疗膀胱功能障碍的药物提供新的靶标。

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