K+ channels in biological processes: vascular K+ channels in the regulation of blood pressure
Matthias E Werner,1 Jonathan Ledoux2–4
1Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK; 2Research Center, Montreal Heart Institute; 3Department of Molecular and Integrative Physiology, 4Department of Medicine, Université de Montréal, Montreal, QC, Canada
Abstract: Appropriate supply of blood to organs and tissues is highly dependent on arterial blood pressure and therein of the peripheral blood vessel resistance. Of the two main components of vessel resistance, the active resistance results from the modulation of the contractility level of vascular smooth muscle cells (VSMCs). The intracellular level of Ca2+ in VSMCs is an essential component of muscle contraction and is tightly regulated through modulation of the membrane potential. Since resting membrane potential of vascular cells is mainly dependent on K+ ions, ion channels permeable to K+ ions have a significant impact on contractility of smooth muscle cells and therefore on vascular diameter and blood pressure. Activation of K+ channels on both endothelial cells and VSMCs is generally associated to hyperpolarization and relaxation of vascular smooth muscle. Several types of K+ channels are expressed in VSMCs and endothelial cells, and they are classified based on their pharmacological and biophysical properties. Voltage-dependent K+ channels are activated by depolarization and are mainly involved in negative-feedback mechanisms. Ca2+-activated K+ channels can be divided into three groups, with BKCa being activated by both intracellular Ca2+ and depolarization. On the other hand, KCa2.x and KCa3.1 channels (small and intermediate Ca2+-activated K+ channels, respectively) are almost strictly dependent on rises in intracellular Ca2+ levels to increase their open probability. Kir and adenosine triphosphate (ATP)-sensitive K+ (KATP) channels, members of the same family, have a significant impact on VSMC membrane potential. The more recently studied two-pore K+ channels are thought to be metabolic sensors (like KATP channels) and would be involved in acute regulation of local blood flow. This review will summarize the main K+ channels expressed in vascular cells and their relevance in the control of vascular tone and blood pressure.
Keywords: membrane potential, Ca2+, vascular tone
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