Role of voltage-gated K+ (Kv) channels in vascular function
Smirnov SV., Tammaro P., Hutchings SR., Smith AL.
Voltage-dependent K+ (Kv) channels represent the most diverse group of K+ channels ubiquitously expressed in vascular smooth muscles. The Kv channels, together with other types of K+ conductances, such as Ca2+-activated (BKCa), ATP-sensitive (KATP), and inward rectifier, play an important role in the control of the cell membrane potential and regulation of the vascular contractility. Comparison of the expression of different Kv channel isoforms obtained from RT-PCR studies showed that virtually all Kv genes could be detected in vascular smooth muscle cells (VSMC). Based on the analysis of both mRNA and protein expressions, it is likely that Kv1.1, Kv1.2, Kv1.3, Kv1.5, Kv1.6, Kv2.1, and Kv3.1b channel isoforms are mainly responsible for the delayed rectifier current characterized electrophysiologically in most VSMC types studied to date. It has been recently demonstrated by our research group and by others that functional expression of multiple Kv channel α-subunits is not homogeneous and varies in different vascular beds of small and large arteries. Growing evidence suggests that in some small arteries, e.g., cerebral arteries and arterioles, the Kv channels are activated at more negative membrane voltages than BKCa, thus making a greater contribution to the control of vascular tone. Our data also suggest that in some blood vessels, such as the rat aorta and mouse small mesenteric arteries, the Kv channel current (identified mainly as passed through Kv2.1 channels), but not BKCa, is the predominant conductance activated even under conditions where intracellular Ca2+ concentration is increased up to 200 nM. In addition, our data indicate that the Kv2.1 channel current could also contribute to the regulation of the induced rhythmic activity in the rat aorta in vitro acting as a negative feedback mechanism for membrane depolarization. We and other experimenters also demonstrated that functional expression of Kv channels is a dynamic process, which is altered under normal physiological conditions (e.g., during the development of the vessels), and in various pathological states (e.g., pulmonary hypertension developing during chronic hypoxia). Recent findings also suggest that activation of Kv channels can also play a role in vascular apoptosis (causing loss of intracellular K+ and subsequent cell shrinking, one of the essential prerequisites of cellular apoptosis). To summarize, the Kv channels are essential for normal vascular function, and their expression and properties are altered under abnormal conditions. Therefore, understanding of the molecular identity of native Kv channels and their functional significance and elucidation of the mechanisms, which govern and control the expression of the Kv channels in the vasculature, represent an important and challenging task and could also lead to the development of useful therapeutic strategies for the treatment of cardiovascular diseases.