The actions of nickel on membrane currents activated by hyperpolarisation in single cells from the rabbit atrioventricular node

1. 1. The atrioventricular node (AVN) is vital for cardiac function as it normally provides the only conduction route for the cardiac impulse from atria to ventricles and can act as a pacemaker for the ventricles if the sinoatrial node (SAN) fails. We have shown previously that whilst 80-90% of AVN myocytes do not possess I_f (we have termed these type I cells), a small proportion (10-20%) of AVN cells (type 2) do exhibit I_f. 2. 2. The present study describes the effects of the divalent cation nickel (Ni) on membrane currents activated by hyperpolarising voltage clamps from -40/mV in type 1 and type 2 cells at 35°C, using the whole cell patch clamp technique. In type 2 cells 5 mM Ni enhanced the amplitude of I_f. At -120 mV the mean Ni-activated I_f was -1.85 ± 0.28 pA/pF (mean ± SEM; n = 5). Ni significantly enhanced I_f at -70 mV and at all potentials negative to this (p < 0.05 at -70, -80, -90 and -110 mV; 0.05 < p < 0.1 at -100 mV; p < 0.005 at -120 mV). 3. 3. In type 1 cells, which exhibit a small time-independent inward current on hyperpolarisation there was no activation of If by Ni (p > 0.1 at all potentials between -40 mV and -120 mV). 4. 4. In type 1 cells 5 mM Ni significantly reduced the time-independent inward current activated by a hyperpolarising pulse to -120 mV (p < 0.02) and had a smaller effect at -110 and -100 mV (0.05 < p < 0.1 at these potentials). With pulses to less negative potentials there was no significant alteration of the time-independent current. 5. 5. An additional observation was that the fast sodium current activated on repolarisation of the membrane potential to -40 mV after a hyperpolarising voltage clamp appeared to be blocked by Ni. However, this apparent blockade reflected a positive shift in the activation threshold for I_Na, since a repolarising step to -30 mV could still elicit I_Na. 6. 6. Ni is known to block sarcolemmal Na/Ca exchange in cardiac cells, and one possible mechanism for the enhancement of I_f by Ni in type 2 cells is increased intracellular Ca via Na/Ca exchange blockade increasing I_f. The reduction in end pulse current in type 1 cells is also consistent with Na/Ca exchange current blockade. A second possibility of the enhanced I_f in type 2 cells with Ni is a positive shift of the activation curve for I_f in the presence of an increased concentration of external divalent cations.