The involvement of lidocaine and tetrodotoxin-sensitive current in the generation of action potentials with low DV/DT max in the cells of the mouse sinoauricular region

The effects of the specific blockers of the inward Na-current --lidocaine and tetrodotoxin (TTX) were studied with microelectrode technique on the spontaneously beating strips of the mouse sinoauricular (SA) area. Lidocaine (25 microM) and TTX (25 pM) increased the duration of the peak of the action potentials (AP) of true pacemaker cells by extending the plateau phase (phase 2 or APD 20), slowing the dV/dt max from 2.6 +/- 0.8 V/s (n = 25) to 1.4 +/- 0.3 V/s (n = 5, p < 0.05) and reducing the velocity of diastolic depolarization (DD) by 20%. The extend of the dV/dt max value decline depended on the lidocaine concentration. The experimental data fully meted to Hill equation. The lidocaine threshold concentration was 20 microM. The lidocaine effective concentration which decreased dV/dt max by 50% (EC50) was 35 microM. The TTX (25 microM) exposure decreased the dV/dt max from 1.6 V/s to 0.8 V/s and DD velocity slowed by 49%. It should be noted that TTX also increased the duration of APD20. Our data show that dV/ dt max of the true pacemaker cells was reduced by 35-45% after exposure to TTX and lidocaine. This fact confirms the involvement of Na-current in the generation of the upstroke true pacemaker cells AP.