Beta-receptor activation increases sodium current in guinea pig heart

Abstract

Aim: To study the influence of β-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.

Electrophysiological mechanisms of sophocarpine as a potential antiarrhythmic agent

“…Each perfusion lasted for about 8-10 min; meanwhile the RP, APA, V max , and APD were measured [7] . The effective refractory period was obtained by an extra super-threshold stimulus, which was applied during different repolarizing phases of the AP.…”

“…The initial large inward current was invoked by depolarization clamping, as shown in Figure 5A. npg As this inward current had been blocked by the special Na + channel blocker TTX 10 μmol/L (not shown), this current could be regarded as I Na [7] . After the cell was perfused with sophocarpine (10 μmol/L), the inward current was decreased substantially.…”

“…Three platinum electrodes, which had been placed on the cardiac apex, right atrium, and aortic root, were used to record the ECG. The signals were documented on a computer with the PowerLab system (PowerLab ML135, ML 785, ADInstruments, Australia) [7] .…”

“…The right ventricular papillary www.chinaphar.com Yang ZF et al Acta Pharmacologica Sinica npg muscles (from guinea pig) or the sinus nodes with partial right atrium (from rabbit) were excised and pinned to the bottom of a recording chamber. The chamber was perfused with Tyrode's solution at a constant rate of 3 mL/min and maintained at a temperature of 37±0.5 °C [7,10] .…”

“…After 30 min of stimulation, transmembrane AP was recorded by a conventional glass microelectrode that was filled with 3 mol/L KCl and had a tip resistance of 15-20 MΩ. The records were sampled and stored in the computer through the amplifier (MEZ8201, Nihon Kohden, Japan) and PowerLab interface (PowerLab ML785, ADInstruments, Australia) [7,10] . The calculated parameters for the fast response AP included the resting potential (RP), the action potential amplitude (APA), the maximal depolarization velocity (V max ), the action potential duration (APD 50 and APD 90 ), and the effective refractory period (ERP).…”