Patho-, physiological roles of voltage-dependent K+ channels in pulmonary arterial smooth muscle cells

Abstract

In this review, we demonstrate the basic properties, modulation of, and pathological changes in voltage-dependent K+ (Kv) channels that are expressed in pulmonary arterial smooth muscle cells (PASMCs). Pulmonary Kv channels are thought to play a crucial role in the maintenance of resting membrane potentials, and therefore the vascular tone of the pulmonary arteries. Although the molecular identity of pulmonary Kv channels is not clear, Kv1.1, Kv1.2, Kv1.5, Kv2.1, Kv9.3, and Kv3.1 subtypes are expressed in PASMCs. In addition, resistant PASMCs contain greater amount of Kv channels as compared to conduit PASMCs. This heterogenetic expression of Kv channels is consistent with regional differences in the contractile response to hypoxia. Similar to other K+ channels, pulmonary Kv channels can also be modulated by several vasoconstrictors concomitant with the activation of protein kinase C (PKC). Alterations in Kv channel function have several additional and interrelated consequences, including the regulation of cell proliferation and apoptosis, which ultimately lead to pulmonary vascular remodeling. Increased pulmonary vasoconstriction in pulmonary arterial hypertension is attributable to decreased expression and activity of Kv channels in smooth muscle cells. Kv channels play a central role in the maintenance of cellular homeostasis and ion channels, and consequential signaling cascades. Therefore, Kv channels are potential therapeutic targets for the treatment of pulmonary vascular disease.