AKAP150 is required for stuttering persistent Ca2+ sparklets and angiotensin II-induced hypertension.

Imagen de Manuel F Navedo
TítuloAKAP150 is required for stuttering persistent Ca2+ sparklets and angiotensin II-induced hypertension.
Publication TypeJournal Article
Year of Publication2008
AutoresNavedo, MF, Nieves-Cintrón, M, Amberg, GC, Yuan, C, V Votaw, S, W Lederer, J, G McKnight, S, Santana, LF
JournalCirc Res
Volume102
Issue2
Paginatione1-e11
Date Published2008 Feb 1
ISSN1524-4571
Palabras claveA Kinase Anchor Proteins, Angiotensin II, Animals, Calcium Channels, L-Type, Calcium Signaling, Hypertension, Mice, Mice, Knockout, Protein Kinase C-alpha, Vascular Resistance
Abstract

Hypertension is a perplexing multiorgan disease involving renal primary pathology and enhanced angiotensin II vascular reactivity. Here, we report that a novel form of a local Ca2+ signaling in arterial smooth muscle is linked to the development of angiotensin II-induced hypertension. Long openings and reopenings of L-type Ca2+ channels in arterial myocytes produce stuttering persistent Ca2+ sparklets that increase Ca2+ influx and vascular tone. These stuttering persistent Ca2+ sparklets arise from the molecular interactions between the L-type Ca2+ channel and protein kinase Calpha at only a few subsarcolemmal regions in resistance arteries. We have identified AKAP150 as the key protein, which targets protein kinase Calpha to the L-type Ca2+ channels and thereby enables its regulatory function. Accordingly, AKAP150 knockout mice (AKAP150-/-) were found to lack persistent Ca2+ sparklets and have lower arterial wall intracellular calcium ([Ca2+]i) and decreased myogenic tone. Furthermore, AKAP150-/- mice were hypotensive and did not develop angiotensin II-induced hypertension. We conclude that local control of L-type Ca2+ channel function is regulated by AKAP150-targeted protein kinase C signaling, which controls stuttering persistent Ca2+ influx, vascular tone, and blood pressure under physiological conditions and underlies angiotensin II-dependent hypertension.

DOI10.1161/CIRCRESAHA.107.167809
Alternate JournalCirc. Res.
PubMed ID18174462
Grant ListHL077115 / HL / NHLBI NIH HHS / United States
HL085870 / HL / NHLBI NIH HHS / United States