Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Coker Life Sciences Building, Room 609D, 715 Sumter Street, Columbia, SC 29208, USA.
Nat Rev Urol. 2011 Dec 13;9(1):30-40. doi: 10.1038/nrurol.2011.194.
Contraction and relaxation of the detrusor smooth muscle (DSM), which makes up the wall of the urinary bladder, facilitates the storage and voiding of urine. Several families of K(+) channels, including voltage-gated K(+) (K(V)) channels, Ca(2+)-activated K(+) (K(Ca)) channels, inward-rectifying ATP-sensitive K(+) (K(ir), K(ATP)) channels, and two-pore-domain K(+) (K(2P)) channels, are expressed and functional in DSM. They control DSM excitability and contractility by maintaining the resting membrane potential and shaping the action potentials that determine the phasic nature of contractility in this tissue. Defects in DSM K(+) channel proteins or in the molecules involved in their regulatory pathways may underlie certain forms of bladder dysfunction, such as overactive bladder. K(+) channels represent an opportunity for novel pharmacological manipulation and therapeutic intervention in human DSM. Modulation of DSM K(+) channels directly or indirectly by targeting their regulatory mechanisms has the potential to control urinary bladder function. This Review summarizes our current state of knowledge of the functional role of K(+) channels in DSM in health and disease, with special emphasis on current advancements in the field.
逼尿肌平滑肌(DSM)的收缩和松弛构成了膀胱的壁,有助于尿液的储存和排空。几种 K(+)通道家族,包括电压门控 K(+)(K(V))通道、Ca(2+)-激活的 K(+)(K(Ca))通道、内向整流型 ATP 敏感的 K(+)(K(ir)、K(ATP))通道和双孔域 K(+)(K(2P))通道,在 DSM 中表达和具有功能。它们通过维持静息膜电位和塑造动作电位来控制 DSM 的兴奋性和收缩性,从而决定了该组织收缩的时相性质。DSM K(+)通道蛋白或参与其调节途径的分子的缺陷可能是某些形式的膀胱功能障碍(如膀胱过度活动症)的基础。K(+)通道代表了在人类 DSM 中进行新型药理学操作和治疗干预的机会。通过靶向其调节机制直接或间接地调节 DSM K(+)通道有可能控制膀胱功能。本综述总结了我们目前对 K(+)通道在健康和疾病中的 DSM 功能作用的了解,特别强调了该领域的最新进展。