Vascular calcium channels and high blood pressure: pathophysiology and therapeutic implications.
Long-lasting Ca(2+) (Ca(L)) channels of the Ca(v)1.2 gene family are heteromultimeric structures that are minimally composed of a pore-forming alpha(1C) subunit and regulatory beta and alpha(2)delta subunits in vascular smooth muscle cells. The Ca(L) channels are the primary pathways for voltage-gated Ca(2+) influx that trigger excitation-contraction coupling in small resistance vessels. Notably, vascular smooth muscle cells of hypertensive rats show an increased expression of Ca(L) channel alpha(1C) subunits, which is associated with elevated Ca(2+) influx and the development of abnormal arterial tone. Indeed, blood pressure per se appears to promote Ca(L) channel expression in small arteries, and even short-term rises in pressure may alter channel expression. Membrane depolarization has been shown to be one stimulus associated with elevated blood pressure that promotes Ca(L) channel expression at the plasma membrane. Future studies to define the molecular processes that regulate Ca(L) channel expression in vascular smooth muscle cells will provide a rational basis for designing antihypertensive therapies to normalize Ca(L) channel expression and the development of anomalous vascular tone in hypertensive pathologies.
Sonkusare
Swapnil
S
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 West Markham Street #611, Little Rock, AR 72205-7199, USA.
Palade
Philip T
PT
Marsh
James D
JD
Telemaque
Sabine
S
Pesic
Aleksandra
A
Rusch
Nancy J
NJ
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D015640:Ion Channel Gating; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011487:Protein Conformation
D000959:Antihypertensive Agents; D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C)