Key result
SC-36602 suppresses Vmax by ~40% and shortens cardiac refractory period in preclinical models.
Why the study?
The electrophysiological properties and membrane potential-dependent effects of the new class I antiarrhythmic agent SC-36602 were not previously characterized in cardiac tissue.
Does SC-36602 affect action potentials in guinea pig papillary muscle?
Does SC-36602 affect action potentials in guinea pig papillary muscle?
SC-36602 is a new class I antiarrhythmic agent that depresses Vmax and shortens the effective refractory period, suggesting it would preferentially depress conduction in depolarized tissue.
Answers are grounded in this paper and cite their sources.
SC-36602 shows class I effects in isolated tissue; leaves open translation to in vivo or clinical antiarrhythmic use.
The in vitro electrophysiological properties of a new class I antiarrhythmic agent, SC-36602, were evaluated by recording action potentials (APs) from guinea pig papillary muscle. SC-36602 and its (+) and (-) enantiomers (10(-6)-10(-4) M) caused a concentration- and only slight frequency-dependent depression of Vmax (maximum rate of rise of the AP). At stimulation rates of 30, 60, 120, and 200 pulses/min, SC-36602 (10(-4) M) reduced Vmax to 64 +/- 2.2, 62 +/- 2.8, 60 +/- 2.4, and 58 +/- 2.7% of control, respectively, and significantly shortened effective refractory period (ERP) (20-40%). The rate constants for onset of block of Vmax during trains of stimuli at 1 or 3.3 Hz were similar (approximately 0.2 AP-1). Slow recovery from Vmax block following a stimulus train recorded in tissue depolarized by 10 mM [K+]o Tyrode's solution was enhanced following exposure to SC-36602. The normalized relationship between Vmax and membrane potential was shifted 3 and 12 mV in the hyperpolarizing direction at stimulation frequencies of 0.2 and 1 Hz, respectively. These results suggest that SC-36602 would preferentially depress conduction in depolarized tissue in vivo.
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Borowicz et al. (1987) studied this question. SC-36602 vs. control was evaluated on Vmax (maximum rate of rise of the action potential). SC-36602 caused a concentration-dependent depression of Vmax (reducing it to 58-64% of control at 10(-4) M) and shortened the effective refractory period by 20-40% in vitro.
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