Pacemaker current, membrane resistance, and K+ in sheep cardiac Purkinje fibres

The pacemaker current in cardiac Purkinje fibres has been attributed to either a decrease in potassium conductance or an increase in a non-specific (Na-K) conductance. The former mechanism would be associated with an increase in membrane resistance (Rm) and the latter with a decrease in Rm. The aim of this study was to obtain evidence in support of one or other mechanism by measuring Rm during the pacemaker current (Idd) under conditions where there is a small or no extracellular potassium depletion.

Hearts were obtained from anaesthetised sheep and thin strands of ventricular Purkinje fibres were shortened to less than or equal to 1.6 mm. Purkinje fibres were voltage clamped to potentials positive and negative to the potassium equilibrium potential (EK) using a two microelectrode technique. Small current pulses were superimposed on Idd to measure Rm changes. Procedures were used that decrease either the background potassium current IKl or Idd in order to dissect changes in Rm due to K depletion from those due to Idd.

Rm increased during Idd, whether the pacemaker current increased or decreased as a function of time. Increasing [K]o from 2.7 to 5.4 mmol.litre-1 decreased Rm and during hyperpolarising steps increased the instantaneous current but did not change Idd amplitude. In 2.7 mmol.litre-1 K, caesium (Cs, 2 mmol.litre-1) increased the holding current (Ih), had little effect on the instantaneous current, and eliminated Idd and associated Rm changes. In 5.4 and 10.8 mmol.litre-1 K, Cs increased Ih and decreased Idd amplitude and in 10.8 mmol.litre-1 K Cs decreased the instantaneous current on hyperpolarisation. If the current was reversed, Cs decreased but did not abolish it. In normal [K]o, barium (Ba, 0.05-0.5 mmol.litre-1) increased Ih and Rm, reduced the instantaneous current but did not increase Idd amplitude. In high [K]o, Ba instead increased the amplitude and rate of development of Idd. When Cs was applied in the presence of Ba, Idd was reduced or eliminated depending on [K]o.

The changes in membrane resistance during the pacemaker current cannot be accounted for by K depletion and suggest that in the range of diastolic depolarisation the pacemaker current results predominantly from a time dependent decrease in K conductance.