α1-Adrenergic Receptors Control the Activity of Sinoatrial Node by Modulating Transmembrane Transport of Chloride Anionsстатья
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Дата последнего поиска статьи во внешних источниках: 15 февраля 2024 г.
Аннотация:Norepinephrine (NE), which is released by sympathetic nerve endings, causes an increase in thefrequency of spontaneous action potentials in the pacemaker cardiomyocytes of the sinoatrial node (SAN) ofthe heart. This results in an increase in heart rate (HR). Two types of postsynaptic adrenoreceptors (ARs),α1-AR and β-AR, mediate the effects of NE. The role of α1-AR in the sympathetic control of heart rate andSAN automaticity, as well as the membrane mechanisms involved in α1-AR-mediated pacemaker control,have not yet been elucidated. In this study, we utilized immunofluorescence confocal microscopy to examinethe distribution of α1A-AR in the SAN of rats. Additionally, we assessed the expression of α1A-AR mRNAin the SAN tissue using RT-PCR. Furthermore, we investigated the impact of α1-AR stimulation on keyfunctional parameters of the pacemaker, including the corrected sinus node recovery time (SNRT/cSNRT)and the SAN accommodation, using the Langendorff perfused heart technique. We also used optical mappingof the electrical activity of perfused, isolated tissue preparations to study the effect of α1-AR stimulationon the spatiotemporal characteristics of SAN excitation. We tested the effects of chloride transmembrane conductanceblockade on alteration of functional parameters and pattern of SAN excitation caused by α1-AR. Fluorescentsignals corresponding to α1A-AR have been identified in SAN cardiomyocytes, indicating the presenceof α1A-AR at protein level. The expression of α1A-AR in SAN has been also confirmed at the mRNAlevel. The stimulation of α1-AR affects SAN functioning. Phenylephrine (PHE) utilized as α1A-AR agonistcaused a decrease in SNRT/cSNRT, as well as an acceleration of SAN accommodation. These effects wererate dependent and were observed in a high frequency range of pacemaker tissue stimulation. PHE induceschanges in the excitation pattern of the SAN. The effects of PHE on functional parameters and SAN excitationpattern are attenuated by Ca2+-dependent chloride channel blocker NPPB but remains unaffected bythe protein kinase C inhibitor BIM. Our results suggest that cardiac α1-ARs are important for maintainingfunction of SAN pacemaker at high heart rates and that α1-AR signalling cascades in the SAN by targetingCa2+-dependent chloride channels are involved in the α1-adrenergic modulation of the electrophysiologicalproperties of the heart pacemaker.