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

Abstract

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.