Resumen
Los canales de calcio dependientes de voltaje son importantes en la contracción inducida por la despolarización de las células de músculo liso vascular de mamíferos. Los canales tipo L y tipo T son los clásicos involucrados en dicho mecanismo. Sin embargo, recientemente hemos demostrado que el gen de la subunidad a2.1, que codifica una isoforma neuronal de canales de calcio dependientes de voltaje (tipo P/Q) también se expresa y contribuye funcionalmente con la contracción en los vasos renales de resistencia. Encontramos expresión de ARN mensajero (ARNm) de la subunidad a2.1 en vasos preglomerulares de rata disecados, en cultivo de células de músculo liso vascular de vasos preglomerulares y en células de músculo liso de aorta (A7r5). Los datos se confirmaron a nivel proteico. El bloqueante específico de los canales de calcio dependientes de voltaje tipo P/Q, w-agatoxina IVA, fue capaz de bloquear la contracción mediada por la despolarización en arteriolas aferentes renales (lo cual reveló la importancia funcional de los canales de calcio tipo P en el mecanismo de contracción), y parece indicar la participación de los canales tipo P, además de los canales tipo L y tipo T, en el mecanismo de excitación y contracción de las células de músculo liso vascular. A su vez, el hallazgo podría constituir un nuevo blanco en la regulación del tono vascular. La demostración de canales de calcio dependientes de voltaje tipo P en células de músculo liso vascular puede ser de importancia en la investigación de diversos fenómenos, como hipertensión, migraña hemipléjica familiar y otras enfermedades que involucran a las células de músculo liso vascular y a los canales dependientes de voltaje.
Palabras clave
Músculo liso, canales de calcio dependientes de voltaje, tipo P, vasos renales de resistencia.
Clasificación en siicsalud
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Especialidades
Principal: Farmacología
Relacionadas: Cardiología, Medicina Interna
Enviar correspondencia a: Pernille B. Hansen, NIDDK, NIH, Building 10, Room 4D50, 10 Center Drive MSC, 1370 Bethesda, MD-20892, USA
Patrocinio y reconocimiento La investigación debe ser atribuida al Department of Physiology and Pharmacology, University of Southern Denmark, Winslowparken 19, 3.sal, DK-5000 Odense, Dinamarca.
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P/Q-TYPE VOLTAGE-DEPENDENT CALCIUM CHANNELS IN VASCULAR SMOOTH MUSCLE CELLS
Abstract
Voltage-dependent Ca2+ channels are important for the depolarization- evoked contraction of mammalian vascular smooth muscle cells. L- and T-type channels are the classical channels involved in the mechanism however, we recently demonstrated that also the a2.1 subunit, which encodes a neuronal isoform of voltage dependent calcium channels (P/Q-type), is expressed and contribute functionally to contraction in renal resistance vessels. We found expression of mRNA for the a2.1 subunit in microdissected rat preglomerular vessels, in cultured smooth muscle cells from preglomerular vessels and aortic smooth muscle cells (A7r5). These data were confirmed at protein level. The specific blocker of P/Q-type voltage-dependent calcium channels w-Agatoxin-IVA was able to block the depolarization-mediated contraction in renal afferent arterioles, revealing the functional importance of P-type calcium channels for the constriction mechanism. This suggests that, in addition to L- and T-type channels also the contribution from P-type channels, should also be considered in the excitation-constriction mechanism in smooth muscle cells and might constitute a new target for regulation of vascular tonus. The demonstration of P-type voltage dependent calcium channels in vascular smooth muscle cells could be important when investigating phenomena as hypertension, familial hemiplegic migraine and other diseases involving smooth muscle cells and voltage dependent calcium channels.
Key words
Smooth muscle, voltage dependent calcium channel, P-type, renal, resistance vessels.
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Bibliografía del artículo
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