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)