title: Membrane potential bistability is controlled by the hyperpolarization-activated current I(H) in rat cerebellar Purkinje neurons in vitro.
abstract: We investigated the role of the hyperpolarization-activated mixed cation current, I(H), 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 I(H). Blockade of I(H) 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 I(H) unmasked a form of membrane potential bistability, where transitions between tonic firing and quiescent states (separated by approximately 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 I(H) by serotonin unmasked bistability, indicating that bistability of Purkinje neurons is likely to occur under physiological conditions. These data indicate that I(H) 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 I(H), 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.
authors.affiliation: Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory 0200, Australia. stephen.williams@anu.edu.au
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Williams
authors.forename: Soren R
authors.initials: SR
authors.lastname: Christensen
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Stuart
authors.forename: Michael
authors.initials: M
authors.lastname: Häusser
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004558:Electric Stimulation; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D015221:Potassium Channels; D011689:Purkinje Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D012701:Serotonin