Role of Potassium Ion Channels in Vascular Tone Regulation and Hypertension.

Madiwila Gamarachchige Tharindika, Thanigaimani Shivshankar, Barratt Kristen S, Golledge Jonathan — Arteriosclerosis, thrombosis, and vascular biology

Abstract

Potassium ion channels are critical regulators of vascular homeostasis and cardiac electrophysiology that act by regulating the resting membrane potential via hyperpolarization or depolarization. They are modulated in response to intracellular or extracellular voltage or ion concentrations, which is key in preserving vascular tone and cardiac contractility. In vascular smooth muscle cells, large-conductance calcium-activated potassium channels are influenced by both intracellular calcium ion concentrations and during depolarization, whereas small- and intermediate-conductance channels are strictly dependent on intracellular calcium ions only, which in turn are regulated by ryanodine receptors of the sarcoplasmic reticulum. On the other hand, voltage-dependent potassium channels are activated by membrane depolarization, and the resting membrane potential is restored via negative feedback. Genome-wide association studies in humans identified variation in genes encoding voltage-dependent and 2-pore domain potassium ion channels as being associated with the risk of developing hypertension. In rodent models of hypertension, arterial expression and activity of large-conductance calcium-activated potassium channels are upregulated, whereas voltage-dependent, ATP-sensitive, and inward-rectifier potassium channels are downregulated. In cardiomyocytes, potassium currents play a key role in regulating cardiac action potential and refractory periods, with their dysregulation contributing to arrhythmogenesis. Given the therapeutic significance of potassium ion channels in antiarrhythmic treatments, we have reviewed their potential to exhibit blood pressure-lowering effects using evidence from human and animal studies. More research is warranted to investigate the significance of existing drugs, including amiodarone and sotalol, in the treatment of hypertension.

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