Beta-receptor activation increases sodium current in guinea pig heart.
OBJECTIVE
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.


CONCLUSIONS
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.
Wang
Hong-wei
HW
Department of Physiology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Yang
Zhi-fang
ZF
Zhang
Yin
Y
Yang
Jian-min
JM
Liu
Yuan-mou
YM
Li
Ci-zhen
CZ
D000200:Action Potentials / Q000187:drug effects; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004562:Electrocardiography; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000166:cytology; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D015222:Sodium Channels / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D015222:Sodium Channels; D000242:Cyclic AMP; D007545:Isoproterenol