Functional role of M-type (KCNQ) K⺠channels in adrenergic control of cardiomyocyte contraction rate by sympathetic neurons.
J Physiol
; 589(Pt 10): 2559-68, 2011 May 15.
Article
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| MEDLINE
| ID: mdl-21486761
ABSTRACT
M-type (KCNQ) K⺠channels are known to regulate excitability and firing properties of sympathetic neurons (SNs), but their role in regulating neurotransmitter release is unclear, requiring further study. We sought to use a physiological preparation in which SNs innervate primary cardiomyocytes to evaluate the direct role of M-channels in the release of noradrenaline (NA) from SNs. Co-cultures of rat SNs and mouse cardiomyocytes were prepared, and the contraction rate (CR) of the cardiomyocyte syncytium monitored by video microscopy. We excited the SNs with nicotine, acting on nicotinic acetylcholine receptors, and monitored the increase in CR in the presence or absence of the specific M-channel opener retigabine, or agonists of bradykinin B2 or purinergic P2Y receptors on the SNs. The maximal adrenergic effect on the CR was determined by application of isoproterenol (isoprenaline). To isolate the actions of B2 or P2Y receptor stimulation to the neurons, we prepared cardiomyocytes from B2 receptor or P2Y2 receptor knock-out mice, respectively. We found that co-application of retigabine strongly decreased the nicotine-induced increase in CR. Conversely, co-application of bradykinin or the P2Y-receptor agonist UTP augmented the nicotine-induced increase in CR to about half of the level produced by isoproterenol. All effects on the CR were wholly blocked by propranolol. Our data support the role of M-type K⺠channels in the control of NA release by SNs at functional adrenergic synapses on cardiomyocytes.We conclude that physiological receptor agonists control the heart rate via the regulation of M-current in SNs.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Sistema Nervioso Simpático
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Miocitos Cardíacos
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Canales de Potasio KCNQ
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Corazón
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Frecuencia Cardíaca
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Contracción Miocárdica
Límite:
Animals
Idioma:
En
Revista:
J Physiol
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos