AKAP150 is required for stuttering persistent Ca2+ sparklets and angiotensin II-induced hypertension.
Enviado por Manuel F Navedo el
Título | AKAP150 is required for stuttering persistent Ca2+ sparklets and angiotensin II-induced hypertension. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Autores | Navedo, MF, Nieves-Cintrón, M, Amberg, GC, Yuan, C, V Votaw, S, W Lederer, J, G McKnight, S, Santana, LF |
Journal | Circ Res |
Volume | 102 |
Issue | 2 |
Pagination | e1-e11 |
Date Published | 2008 Feb 1 |
ISSN | 1524-4571 |
Palabras clave | A 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. |
DOI | 10.1161/CIRCRESAHA.107.167809 |
Alternate Journal | Circ. Res. |
PubMed ID | 18174462 |
Grant List | HL077115 / HL / NHLBI NIH HHS / United States HL085870 / HL / NHLBI NIH HHS / United States |