| Autor: |
Ivanova, Alexandra D., Filatova, Tatiana S., Abramochkin, Denis V., Atkinson, Andrew, Dobrzynski, Halina, Kokaeva, Zarema G., Merzlyak, Ekaterina M., Pustovit, Ksenia B., Kuzmin, Vladislav S. |
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| Zdroj: |
Acta Physiologica; Apr2021, Vol. 231 Issue 4, p1-17, 17p, 2 Color Photographs, 1 Chart, 6 Graphs |
| Abstrakt: |
Aim: This study is aimed at investigation of electrophysiological effects of α1‐adrenoreceptor (α1‐AR) stimulation in the rat superior vena cava (SVC) myocardium, which is one of the sources of proarrhythmic activity. Methods: α1‐ARs agonists (phenylephrine—PHE or norepinephrine in presence of atenolol—NE + ATL) were applied to SVC and atrial tissue preparations or isolated cardiomyocytes, which were examined using optical mapping, glass microelectrodes or whole‐cell patch clamp. α1‐ARs distribution was evaluated using immunofluorescence. Kir2.X mRNA and protein level were estimated using RT‐PCR and Western blotting. Results: PHE or NE + ATL application caused a significant suppression of the conduction velocity (CV) of excitation and inexcitability in SVC, an increase in the duration of electrically evoked action potentials (APs), a decrease in the maximum upstroke velocity (dV/dtmax) and depolarization of the resting membrane potential (RMP) in SVC to a greater extent than in atria. The effects induced by α1‐ARs activation in SVC were attenuated by protein kinase C inhibition (PKC). The whole‐cell patch clamp revealed PHE‐induced suppression of outward component of IK1 inward rectifier current in isolated SVC, but not atrial myocytes. These effects can be mediated by α1A subtype of α‐ARs found in abundance in rat SVC. The basal IK1 level in SVC was much lower than in atria as a result of the weaker expression of Kir2.2 channels. Conclusion: Therefore, the reduced density of IK1 in rat SVC cardiomyocytes and sensitivity of this current to α1A‐AR stimulation via PKC‐dependent pathways might lead to proarrhythmic conduction in SVC myocardium by inducing RMP depolarization, AP prolongation, CV and dV/dtmax decrease. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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