TRP Channels Mediated Pathological Ca(2+)-Handling and Spontaneous Ectopy

TRP通道介导的病理性Ca(2+)处理和自发性异位搏动

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Abstract

Ion channel biology offers great opportunity in identifying and learning about cardiac pathophysiology mechanisms. The discovery of transient receptor potential (TRP) channels is an add-on to the opportunity. Interacting with numerous signaling pathways, being activated multimodally, and having prescribed signatures underlining acute hemodynamic control and cardiac remodeling, TRP channels regulate cardiac pathophysiology. Impaired Ca(2+)-handling cause contractile abnormality. Modulation of intracellular Ca(2+) concentration ([Ca(2+)](i)) is a major part of Ca(2+)-handling processes in cardiac pathophysiology. TRP channels including TRPM4 regulate [Ca(2+)](i), Ca(2+)-handling and cardiac contractility. The channels modulate flux of divalent cations, such as Ca(2+) during Ca(2+)-handling and cardiac contractility. Seminal works implicate TRPM4 and TRPC families in intracellular Ca(2+) homeostasis. Defective Ca(2+)-homeostasis through TRP channels interaction with Ca(2+)-dependent regulatory proteins such as sodium calcium exchanger (NCX) results in abnormal Ca(2+) handling, contractile dysfunction and in spontaneous ectopy. This review provides insight into TRP channels mediated pathological Ca(2+)-handling and spontaneous ectopy.

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