POSSIBLE INVOLVEMENT OF ALTERED NA-CA2+ EXCHANGE IN NEGATIVE INOTROPIC EFFECTS OF CLASS-I ANTIARRHYTHMIC DRUGS ON RABBIT AND RAT VENTRICLES()

We investigated the way in which Na+ channel blocking class I antiarrh ythmic drugs, lidocaine (30 mu M), flecainide (30 mu M), and RS-2135 ( 100 mu M) affected contractions elicited by several protocols in rat a nd rabbit ventricular strips, Rabbit ventricles showed a positive forc e-frequency relation, and antiarrhythmic drugs inhibited the contracti on, flattening the force-frequency curve. In contrast, rat ventricles showed a negative force-frequency relation, and the drugs shifted the force-frequency curve downward. Rapid-cooling contracture (RCC) also s howed a positive or negative dependence on the frequency of preceding stimulation in rabbit or rat ventricles, respectively. All drugs inhib ited the RCC, suggesting that they reduced the Ca2+ content in the sar coplasmic reticulum. Ryanodine (1 mu M) abolished the RCC in both musc les and the contraction in rat muscles, but partially decreased contra ctions at high frequencies in rabbit ventricles. Antiarrhythmic drugs caused a further inhibition of contractions in the presence of ryanodi ne in rabbit ventricles. These results indicate that inhibition of Na channels by antiarrhythmic drugs alters Na+-Ca2+ exchange, resulting in a decrease in the Ca2+ content in the sarcoplasmic reticulum (SR) a nd the Ca2+ entry through the exchanger.