Pathophysiology of voltage-gated K+ channels in vascular smooth muscle cells: modulation by protein kinases.
In this review, the pathological alteration and clinical relevance of voltage-gated K(+) (Kv) channels and their specific regulation by protein kinase-dependent signaling in vascular smooth muscle cells are described, particularly focusing on the pulmonary vasculature. The physiological relevance, channel characteristics, pharmacological modulation, and expression of Kv channels vary between different arterial beds and between subdivisions of arteries within those vascular beds. Although detailed signaling cascades regulating Kv channels are not clearly elucidated, it is known that the Kv channels in vascular smooth muscle cells can be tightly regulated by protein kinases C (PKC) and A (PKA). Alterations in Kv channel expression and function has been noted in pathological and pathophysiological conditions including hypertension (pulmonary and systemic), in diabetes and in individuals subjected to prolonged hypoxia (high altitude living). Vascular Kv channels are potential therapeutic targets in diseases such as pulmonary arterial hypertension and, therefore, it is important to understand the specific pharmacological modulation of Kv channel isoforms in different vascular beds.
Ko
Eun A
EA
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, FIRST Mitochondrial Research Group, Inje University, 633-165 Gaegeum-dong, Busanjin-gu, Busan 614-735, Republic of Korea.
Park
Won Sun
WS
Firth
Amy L
AL
Kim
Nari
N
Yuan
Jason X-J
JX
Han
Jin
J
D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*; D065627:Familial Primary Pulmonary Hypertension; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*
D024642:Potassium Channels, Voltage-Gated; D011494:Protein Kinases