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 If (we have termed these type 1 cells), a small proportion (10-20%) of AVN cells (type 2) do exhibit If. 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 degrees C, using the whole cell patch clamp technique. In type 2 cells 5 mM Ni enhanced the amplitude of If. At -120 mV the mean Ni-activated If was -1.85 +/- 0.28 pA/pF (mean +/- SEM; n = 5). Ni significantly enhanced If 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. 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. 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. 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 INa, since a repolarising step to -30 mV could still elicit INa. 6. Ni is known to block sarcolemmal Na/Ca exchange in cardiac cells, and one possible mechanism for the enhancement of If by Ni in type 2 cells is increased intracellular Ca via Na/Ca exchange blockade increasing If. 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 If in type 2 cells with Ni is a positive shift of the activation curve for If in the presence of an increased concentration of external divalent cations.
