Role of voltage-gated K<sup>+</sup>(K<inf>v</inf>) 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 Kvchannels, 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 Kvchannel isoforms obtained from RT-PCR studies showed that virtually all Kvgenes 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 Kvchannel 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 Kvchannels 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 Kvchannel 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 Kvchannels 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 Kvchannels 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 Kvchannels are essential for normal vascular function, and their expression and properties are altered under abnormal conditions. Therefore, understanding of the molecular identity of native Kvchannels and their functional significance and elucidation of the mechanisms, which govern and control the expression of the Kvchannels 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.