Takagi Hiroaki, Hashitani Hikaru
Departmentof Cell Physiology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Departmentof Cell Physiology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Eur J Pharmacol. 2016 Oct 15;789:179-186. doi: 10.1016/j.ejphar.2016.07.041. Epub 2016 Jul 25.
The modulation of spontaneous excitability in detrusor smooth muscle (DSM) upon the pharmacological activation of different populations of K(+) channels was investigated. Effects of distinct K(+) channel openers on spontaneous action potentials in DSM of the guinea-pig bladder were examined using intracellular microelectrode techniques. NS1619 (10μM), a large conductance Ca(2+)-activated K(+) (BK) channel opener, transiently increased action potential frequency and then prevented their generation without hyperpolarizing the membrane in a manner sensitive to iberiotoxin (IbTX, 100nM). A higher concentration of NS1619 (30μM) hyperpolarized the membrane and abolished action potential firing. NS309 (10μM) and SKA31 (100μM), small conductance Ca(2+)-activated K(+) (SK) channel openers, dramatically increased the duration of the after-hyperpolarization and then abolished action potential firing in an apamin (100nM)-sensitive manner. Flupirtine (10μM), a Kv7 channel opener, inhibited action potential firing without hyperpolarizing the membrane in a manner sensitive to XE991 (10μM), a Kv7 channel blocker. BRL37344 (10μM), a β3-adrenceptor agonist, or rolipram (10nM), a phosphodiesterase 4 inhibitor, also inhibited action potential firing. A higher concentration of rolipram (100nM) hyperpolarized the DSM and abolished the action potentials. IbTX (100nM) prevented the rolipram-induced blockade of action potentials but not the hyperpolarization. BK and Kv7 channels appear to predominantly contribute to the stabilization of DSM excitability. Spare SK channels could be pharmacologically activated to suppress DSM excitability. BK channels appear to be involved in the cyclic AMP-induced inhibition of action potentials but not the membrane hyperpolarization.
研究了不同类型钾通道药理学激活后对逼尿肌平滑肌（DSM）自发兴奋性的调节作用。使用细胞内微电极技术，检测了不同钾通道开放剂对豚鼠膀胱逼尿肌平滑肌自发动作电位的影响。大电导钙激活钾（BK）通道开放剂NS1619（10μM）可短暂增加动作电位频率，随后阻止动作电位产生，且不会使膜超极化，该作用对iberiotoxin（IbTX，100nM）敏感。较高浓度的NS1619（30μM）使膜超极化并消除动作电位发放。小电导钙激活钾（SK）通道开放剂NS309（10μM）和SKA31（100μM）可显著增加超极化后电位的持续时间，随后以对蜂毒明肽（100nM）敏感的方式消除动作电位发放。电压门控钾通道Kv7开放剂氟吡汀（10μM）可抑制动作电位发放，且不会使膜超极化，该作用对Kv7通道阻滞剂XE991（10μM）敏感。β3肾上腺素能受体激动剂BRL37344（10μM）或磷酸二酯酶4抑制剂咯利普兰（10nM）也可抑制动作电位发放。较高浓度的咯利普兰（100nM）使逼尿肌平滑肌超极化并消除动作电位。IbTX（100nM）可阻止咯利普兰诱导的动作电位阻断，但不能阻止超极化。BK通道和Kv7通道似乎在很大程度上有助于维持逼尿肌平滑肌兴奋性的稳定。备用的SK通道可通过药理学激活来抑制逼尿肌平滑肌的兴奋性。BK通道似乎参与了环磷酸腺苷诱导的动作电位抑制，但不参与膜超极化。
