Ion channels and vascular tone

Abstract

Ion channels in the plasma membrane of vascular muscle cells that form the walls of resistance arteries and arterioles play a central role in the regulation of vascular tone. Current evidence indicates that vascular smooth muscle cells express at least 4 different types of K(+) channels, 1 to 2 types of voltage-gated Ca(2+) channels, >/=2 types of Cl(-) channels, store-operated Ca(+) (SOC) channels, and stretch-activated cation (SAC) channels in their plasma membranes, all of which may be involved in the regulation of vascular tone. Calcium influx through voltage-gated Ca(2+), SOC, and SAC channels provides a major source of activator Ca(2+) used by resistance arteries and arterioles. In addition, K(+) and Cl(-) channels and the Ca(2+) channels mentioned previously all are involved in the determination of the membrane potential of these cells. Membrane potential is a key variable that not only regulates Ca(+2) influx through voltage-gated Ca(2+) channels, but also influences release of Ca(2+) from internal stores and Ca(2+)- sensitivity of the contractile apparatus. By controlling Ca(2+) delivery and membrane potential, ion channels are involved in all aspects of the generation and regulation of vascular tone.

Figure 1

K⁺ channels and vascular tone. Schematic of a vascular smooth muscle cell (top) and cross sections through an arteriole (bottom) that shows that opening K⁺ channels leads to diffusion of K⁺ ions out of the cell, membrane hyperpolarization, closure of voltage-gated Ca²⁺ channels, decreased intracellular Ca^2+, etc (see text), which leads to vasodilatation. Closure of K⁺ channels has the opposite effect. Modified from Jackson.

Figure 2

Cl⁻ channels and vascular tone. Schematic of a vascular smooth muscle cell (top) and cross sections through an arteriole (bottom) that shows that opening of Cl⁻ channels leads to diffusion of Cl⁻ ions out of the cell, membrane depolarization, opening of voltage-gated Ca²⁺ channels, increased intracellular Ca^2+, etc (see text), which leads to vasoconstriction. Closure of Cl⁻ channels has the opposite effect.

Figure 3

Ion channels and vascular tone. Schematic of a cross section through part of a vascular muscle cell. Along the top membrane are shown K_IR, K_ATP, K_V, and BK_Ca channels. Also shown are voltage-gated Ca²⁺ channels, 2 types of Cl⁻ channels (see text), SOC channels (SOCC), and SAC channels (SACC). Shown in the membranes of the sarcoplasmic reticulum (SR) are ryanodine receptors (RyR) and inositol 1,4,5-trisphosphate receptors (IP₃R). Bottom, A few of the signals that are known to modulate the function of the ion channels depicted. AC indicates adenylate cyclase; PKA, cAMP-dependent protein kinase; sGC, soluble guanylate cyclase; PKG, cGMP-dependent protein kinase; EETs, epoxyeicostetraenoic acid (epoxides of arachidonic acid; see text); PLC,phospho-lipase C; DAG,diacylglycerol; PKC=protein kinase C; and 20-HETE, 20-OH-arachidonic acid. See text for details.