Journal
ACTA PHARMACOLOGICA SINICA
Volume 30, Issue 8, Pages 1115-1122Publisher
ACTA PHARMACOLOGICA SINICA
DOI: 10.1038/aps.2009.96
Keywords
sodium-channel current; isoprenaline; cAMP; single channel recording; action potential; ECG; pumping strength
Funding
- Science Foundation of the Shanghai Education Committee [05BZ12, 2005JY01]
- Shanghai Science Committee Foundation [06JC14045]
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Aim: To study the influence of beta-receptor activation on sodium channel current and the physiological significance of increased sodium current with regard to the increased cardiac output caused by sympathetic excitation. Methods: Multiple experimental approaches, including ECG, action potential recording with conventional microelectrodes, whole-cell current measurements, single-channel recordings, and pumping-force measurements, were applied to guinea pig hearts and isolated ventricular myocytes. Results: Isoprenaline was found to dose-dependently shorten QRS waves, increase the amplitude and the V-max of action potentials, augment the fast sodium current, and increase the occurrence frequencies and open time constants of the long-open and burst modes of the sodium channel. Increased levels of membrane-permeable cAMP have similar effects. In the presence of a calcium channel blocker, TTX reversed the increased pumping force produced by isoprenaline. Conclusion: Beta-adrenergic modulation increases the inward sodium current and accelerates the conduction velocity within the ventricles by changing the sodium channel modes, which might both be conducive to the synchronous contraction of the heart and enhance its pumping function.
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