Objective Idiopathic ventricular tachycardia mainly originates from right ventricular outflow tract. It has been proved that cardiomyocytes in rabbit right ventricular outflow tract (RVOT), where early after depolarisation (EAD) could be observed, has significant dispersions in action potential duration (APD) and less steady-state current. The two-pore domain potassium channel (K2p) current, one of the main currents composing the steady-state current, plays an important role in stabilising resting membrane potential, expediting repolarisation and controlling the excitability of cardiomyocytes. The electrophysiological basis of idiopathic ventricular tachycardia arising from right ventricular outflow tract (RVOT-VT) has been seldom reported experimentally. The aim of the experiment was to explore the difference of IK2p between RVOT and free right ventricular wall (RV) myocardial cells in rabbit heart and possible mechanism of the ventricular tachycardia originated from RVOT (RVOT-VT)
Methods The current of rabbit cardiomyocytes in RVOT and in right ventricular (RV) was recorded by the whole-cell patch-clamp technique. The effect of Chloroform, a specific activator of TREK-1, and high pH, an activator of TASK-1, on the currents were tested respectively. TREK-1 and TASK are subtypes of K2p.
Results The steady-state current, which was identified by adding 4-AP to the pipette solution to inhibit Ito and IKur and by adding CdCl2 and TEA to the bathing solution to inhibit ICa2+ and IK1, respectively, was elicited by depolarising potentials. The steady-state current in RVOT myocytes was less than that in RV: at+70mv, the current density below 1pA/pF (n=25) took up 20% in RVOT, while it was rarely found in RV. Further research on the steady-state current showed that K2p current existed in rabbit RV and RVOT myocardial cells. Adding 0.1 mmol/l Quinidine, a known inhibitor of K2p current, to the bathing solution induced a notable decrease of steady-state outward current with depolarisation in both RVOT myocytes and RV myocytes, and the reduction measured at +60 mv in RVOT was 0.41±0.17 pA/pF (n=25) compared with that in RV was 0.57±0.19 pA/pF (n=20), p<0.05. Application of 0.2 mmol/l; Chloroform produced a strong increase of the steady-state current in RV myocytes, and the increment was 0.52±0.11 pA/pF (n=5) at +60 mv. The augmentation of pH to 8.3 by applying NaOH to the bath solution also generated a similar effect.
Conclusion It was the first time on the electrophysiological level verified the existence of the K2p current in rabbit right ventricular myocytes, and further confirmed the subtypes were TREK-1 and TASK-1. The low K2p current density in partial RVOT myocytes leading to lower steady-state current and prolonged APD in RVOT myocytes might be responsible for inducing EAD and resulting in the genesis of RVOT-VT.