Kv channels and vascular smooth muscle cell proliferation

Abstract

Kv channels are present in virtually all VSMCs and strongly influence contractile responses. However, they are also instrumental in the proliferative, migratory, and secretory functions of synthetic, dedifferentiated VSMCs upon PM. In fact, Kv channels not only contribute to all these processes but also are active players in the phenotypic switch itself. This review is focused on the role(s) of Kv channels in VSMC proliferation, which is one of the best characterized functions of dedifferentiated VSMCs.VSMC proliferation is a complex process requiring specific Kv channels at specific time and locations. Their identification is further complicated by their large diversity and the differences in expression across vascular beds. Of interest, both conserved changes in some Kv channels and vascular bed-specific regulation of others seem to coexist and participate in VSMC proliferation through complementary mechanisms.Such a system will add flexibility to the process while providing the required robustness to preserve this fundamental cellular response. K E Y W O R D Scell cycle regulation, phenotypic modulation, potassium channels, vascular remodeling, vascular smooth muscle cell proliferation | THE MULTIPLE PHENOTYPES OF VASCULAR SMOOTH MUSCLE CELLSVSMCs in the vessel wall express a unique repertoire of contractile proteins, signaling molecules, receptors, and ion channels and exhibit extremely low rates of proliferation, migration, and production of ECM proteins. However, VSMCs maintain significant plasticity even in adult animal. In response to changes in environmental cues, VSMCs switch from their contractile, differentiated phenotype to a dedifferentiated, synthetic, and proliferative phenotype. This process, known as PM or phenotypic switching, entails profound structural and functional changes involving changes in gene expression and signaling mecha- 3-7The contractile state is controlled by multiple transcriptional factors, being SRF the best characterized. SRF binds to a specific cis-element, the CArG box, present in the promoter region of target genes. While most VSMC differentiation marker genes contain one or multiple CArG elements, CArG-SRF complexes can also modulate the expression of proliferation-related genes. 8,9 Specificity of these regulatory mechanisms depends on the expression of myocardin, a SRF coactivator expressed exclusively in SMCs and cardiomyocytes. 10-12Myocardin expression is dramatically reduced in cultured SMC, in contrast to the constant levels of SRF with SMC phenotypic modulation.Understanding myocardin function will permit to understand the normal VSMC differentiation and also PM.13

Ion Channels and Their Regulation in Vascular Smooth Muscle

“…By setting and controlling the membrane potential, these channels influence the levels of [Ca 2+ ] i and therefore, vascular smooth muscle contraction. Intriguingly, a subset of K + channels has also been linked to regulation of vascular smooth muscle proliferation (see recent review on this topic in [27,28]). Vascular smooth muscle cells express a wide variety of isoforms from several classes of K + channels, including K V , BK Ca , and K ir channels (see Figure 2).…”

Exercise and Ion-Channel Remodeling in Vascular Smooth Muscle During Hypertension: Therapeutic Implications

“…The K V channel accessory subunits exhibit a variety of protein structures, including integral membrane proteins with additional NH 2 -and COOH-terminal sequences extending into the extracellular and intracellular space, and cytosolic proteins binding to cytoplasmic domains of K V channel α-subunits [57]. The K V family members can be grouped into 12 different subfamilies (K V 1-K V 12), which are encoded by almost 90 ion-channel genes (from resistance to conduit arteries) [48]. In general, membrane depolarization can activate K V channels, hyperpolarizing membrane potential and facilitating the relaxation of small arteries and resistance arterioles.…”

Regulation of microvascular function by voltage‐gated potassium channels: New tricks for an “ancient” dog

“…Byron and Brueggemann (UMIC‐2017‐0064; K V 7 potassium channels as signal transduction intermediates in the control of microvascular tone) provide a comprehensive examination of the emerging, yet increasingly controversial role of K V 7 channels in the control of vascular smooth muscle function and vascular excitability. Lopez‐Lopez and colleagues (UMIC‐2017‐0069; K V channels in vascular smooth muscle cell proliferation) argue that the expression and function of specific K V subunits contribute, through unique mechanisms, to vascular smooth muscle cell proliferation and migration, as well as the phenotypic switching that may occur during pathological conditions. Nishijima and colleagues (UMIC‐2017‐0091; K V 1 channel expression and vasomotor function in human coronary resistance arteries) report a distinctive study examining the expression, function, and regulation of K V channels in human coronary vascular smooth muscle that may reveal unique mechanisms modulating these channels in the human vasculature.…”