One significant factor contributing to the heterogeneity of action potential waveforms in rat left ventricle is a differential distribution of a Ca+ independent transient outward K+ current, I(t). Regional differences in action potential duration have important implications for the gradient of repolarisation in rat left ventricle, for the genesis of the T wave of the electrocardiogram, and for both electrical and mechanical restitution (refractoriness).

1 The effects of quinidine on calcium-independent outward K+ currents in rat ventricular myocytes were studied using whole-cell patch clamp techniques.2 Quinidine sulphate (6 pLM) significantly prolonged repolarization of the ventricular action potential.This effect was larger during early repolarization (25% level) than at later times (90% level

1 Toluene is an industrial solvent widely used as a drug of abuse, which can produce sudden sniffing death due to cardiac arrhythmias. In this paper, we tested the hypothesis that toluene inhibits cardiac sodium channels in Xenopus laevis oocytes transfected with Na v 1.5 cDNA and in isolated rat ventricular myocytes. 2 In oocytes, toluene inhibited sodium currents (I Na þ ) in a concentration-dependent manner, with an IC 50 of 274 mM (confidence limits: 141 -407mM). The inhibition was complete, voltage-independent, and slowly reversible. 3 Toluene had no effect on: (i) the shape of the I -V curves; (ii) the reversal potential of Na þ ; and (iii) the steady-state inactivation. 4 The slow recovery time constant from inactivation of I Na þ decreased with toluene exposure, while the fast recovery time constant remained unchanged. 5 Block of I Na þ by toluene was use-and frequency-dependent. 6 In rat cardiac myocytes, 300 mM toluene inhibited the sodium current (I Na þ ) by 62%; this inhibition was voltage independent. 7 These results suggest that toluene binds to cardiac Na þ channels in the open state and unbinds either when channels move between inactivated states or from an inactivated to a closed state. 8 The use-and frequency-dependent block of I Na þ by toluene might be responsible, at least in part, for its arrhythmogenic effect.

1 The electrophysiological eects of the anti-malarial drug primaquine on cardiac Na + channels were examined in isolated rat ventricular muscle and myocytes. 2 In isolated ventricular muscle, primaquine produced a dose-dependent and reversible depression of dV/dt during the upstroke of the action potential. 3 In ventricular myocytes, primaquine blocked I Na + in a dose-dependent manner, with a K d of 8.2 mM. 4 Primaquine (i) increased the time to peak current, (ii) depressed the slow time constant of I Na + inactivation, and (iii) slowed the fast component for recovery of I Na + from inactivation. 5 Primaquine had no eect on: (i) the shape of the I ± V curve, (ii) the reversal potential for Na + , (iii) the steady-state inactivation and g Na + curves, (iv) the fast time constant of inactivation of I Na + , and (v) the slow component of recovery from inactivation. 6 Block of I Na + by primaquine was use-dependent. Data obtained using a post-rest stimulation protocol suggested that there was no closed channel block of Na + channels by primaquine. 7 These results suggest that primaquine blocks cardiac Na + channels by binding to open channels and unbinding either when channels move between inactivated states or from an inactivated state to a closed state. 8 Cardiotoxicity observed in patients undergoing malaria therapy with aminoquinolines may therefore be due to block of Na + channels, with subsequent disturbances of impulse conductance and contractility.

Our data suggest that I(Ca(TTX))-like current in PMI myocytes does not arise from classical Na(+) channels modified by oxidative stress or PKA phosphorylation and most probably represents a different Na(+) channel type re-expressed in some cells after remodelling.