Membrane potential bistability is controlled by the hyperpolarization-activated current IH in rat cerebellar Purkinje neurons in vitro

Abstract

We investigated the role of the hyperpolarization-activated mixed cation current, IH, in the control of spontaneous action potential firing of rat cerebellar Purkinje neurons in brain slices. Extracellular recordings revealed that the continual action potential firing of Purkinje neurons was disrupted by the pharmacological blockade of IH. Blockade of IH revealed spontaneous transitions between periods of tonic action potential firing and quiescence, without effects on the frequency or variance of action potential generation. Whole-cell recordings revealed that blockade of IH unmasked a form of membrane potential bistability, where transitions between tonic firing and quiescent states (separated by ∼20 mV) were evoked by excitatory and inhibitory postsynaptic potentials, or by the delivery of brief (20 ms) somatic or dendritic positive and negative current pulses. The stable upper state of tonic action potential firing was maintained by the recruitment of axo-somatic voltage-activated sodium, but not calcium, channels. Negative modulation of IH by serotonin unmasked bistability, indicating that bistability of Purkinje neurons is likely to occur under physiological conditions. These data indicate that IH acts as a 'safety net', maintaining the membrane potential of Purkinje neurons within the range necessary for the generation of tonic action potential firing. Following the downregulation of IH, synaptic inhibition can generate long periods (seconds) of quiescence, the duration of which can be controlled by climbing fibre activation and by the underlying 'tone'of parallel fibre activity.