Faculty Bibliography

1. The mechanism of oscillations at low membrane potentials in Purkinje fibres has been investigated using voltage clamp experiments.2. The oscillations are generated by time-dependent variations in an outward current component, i(x1), that is activated over the voltage range -40 to 10 mV. During normal activity, this current is responsible for initiating full repolarization to the resting potential (Noble & Tsien, 1969b) so that the oscillations represent a failure of the normal repolarization process, probably as a consequence of a small change in background (leakage) current.3. These oscillations are distinct from the normal pacemaker activity of Purkinje fibres which is generated by a separate time-dependent current, i(K2) (Noble & Tsien, 1968). i(K2) shows no time-dependence when the membrane potential variations are entirely positive to -65 mV and cannot, therefore, be involved in the oscillatory activity apart from contributing a background outward current.4. The amplitude and frequency of the oscillations are very sensitive to applied currents less than 1 muA/cm(2). Larger currents abolish the oscillatory activity.5. The mechanism of the oscillations is discussed in relation to the possible mechanisms underlying the natural pacemaker activity of the sino-atrial (SA) node

The pacemaker potential in Purkinje fibers is generated by a slow fall in potassium current which allows the inward background currents to depolarize the membrane. Adrenaline shifts the relation between activation of the potassium current and membrane potential in a depolarizing direction. Consequently, during the pacemaker potential, the potassium current falls more rapidly to lower values and the inward currents then depolarize the membrane more quickly. The shift in the potassium activation curve produced by adrenaline is large compared to that produced by calcium ions. The molecular action of adrenaline may involve either a large change in the surface charge of the membrane or a change in the dependence of the potassium permeability on the local electric field

1. The reversal potential of the slow outward current in Purkinje fibres varies with [K](o) in accordance with the expected potassium equilibrium potential. It is concluded that virtually all of this current is carried by potassium ions.2. The magnitude of the current is determined by two separable factors. The first factor is directly proportional to a variable obeying first-order voltage-dependent kinetics of the Hodgkin-Huxley type but with extremely long time constants. The time constants of this variable are extremely sensitive to temperature and the Q(10) over the range 26-38 degrees C is 6.3. The second factor shows inward-going rectification with a marked negative slope in the current-voltage relation beyond about 25 mV positive to the K equilibrium potential. The current-voltage relations measured at different values of [K](o) cross each other on the outward current side of the equilibrium potential.4. The changes in slow potassium current during pace-maker activity have been calculated. It is shown that the mechanism of the pace-maker potential differs in several important respects from that described by Noble's (1962) model. The negative slope in the current-voltage relation appears to be an important factor in generating the last phase of pace-maker depolarization.5. The role of the slow potassium current during the action potential and the consequences of the high temperature dependence of the kinetics are discussed