Properties of a hyperpolarization-activated cation current and its role in rhythmic oscillation in thalamic relay neurones.
1. The physiological and functional features of time-dependent anomalous rectification activated by hyperpolarization and the current which underlies it, Ih, were examined in guinea-pig and cat thalamocortical relay neurones using in vitro intracellular recording techniques in thalamic slices. 2. Hyperpolarization of the membrane from rest with a constant-current pulse resulted in time-dependent rectification, expressed as a depolarizing sag of the membrane potential back towards rest. Under voltage clamp conditions, hyperpolarizing steps to membrane potentials negative to approximately -60 mV were associated with the activation of a slow inward current, Ih, which showed no inactivation with time. 3. The activation curve of the conductance underlying Ih was obtained through analysis of tail currents and ranged from -60 to -90 mV, with half-activation occurring at -75 mV. The time course of activation of Ih was well fitted by a single-exponential function and was strongly voltage dependent, with time constants ranging from greater than 1-2 s at threshold to an average of 229 ms at -95 mV. The time course of de-activation was also described by a single-exponential function, was voltage dependent, and the time constant ranged from an average of 1000 ms at -80 mV to 347 ms at -55 mV. 4. Raising [K+]o from 2.5 to 7.5 mM enhanced, while decreasing [Na+]o from 153 to 26 mM reduced, the amplitude of Ih. In addition, reduction of [Na+]o slowed the rate of Ih activation. These results indicate that Ih is carried by both Na+ and K+ ions, which is consistent with the extrapolated reversal potential of -43 mV. Replacement of Cl- in the bathing medium with isethionate shifted the chloride equilibrium potential positive by approximately 30-70 mV, evoked an inward shift of the holding current at -50 mV, and resulted in a marked reduction of instantaneous currents as well as Ih, suggesting a non-specific blocking action of impermeable anions. 5. Local (2-10 mM in micropipette) or bath (1-2 mM) applications of Cs+ abolished Ih over the whole voltage range tested (-60 to -110 mV), with no consistent effects on instantaneous currents. Barium (1 mM, local; 0.3-0.5 mM, bath) evoked a steady inward current, reduced the amplitude of instantaneous currents, and had only weak suppressive effects on Ih. 6. Block of Ih with local application of Cs+ resulted in a hyperpolarization of the membrane from the resting level, a decrease in apparent membrane conductance, and a block of the slow after-hyperpolarization that appears upon termination of depolarizing membrane responses, indicating that Ih contributes substantially to the resting and active membrane properties of thalamocortical relay neurones.(ABSTRACT TRUNCATED AT 400 WORDS)
McCormick
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Section of Neuroanatomy, Yale University School of Medicine, New Haven, CT 06510.
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D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002412:Cations / Q000494:pharmacology; D002415:Cats; D002712:Chlorides / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D011188:Potassium / Q000502:physiology; D012964:Sodium / Q000502:physiology; D013787:Thalamic Nuclei / Q000502:physiology; D013788:Thalamus / Q000502:physiology*; D013997:Time Factors
D002412:Cations; D002712:Chlorides; D007473:Ion Channels; D012964:Sodium; D011188:Potassium