HYPERPOLARIZATION-ACTIVATED INWARD CURRENT IN HISTAMINERGIC TUBEROMAMMILLARY NEURONS OF THE RAT HYPOTHALAMUS

1. Intracellular recordings were obtained from histaminergic tuberomammillary (TM) neurons of rat hypothalamus in an in vitro slice preparation. The properties of a time- and voltage-dependent inward current activated on hyperpolarization, I(h), were studied by use of the single-electrode voltage-clamp technique. 2. The activation curve of I(h) was well fit by a sigmoidal function, with half-maximal activation occurring at -98 +/- 6 mV. 3. The estimated reversal potential of I(h) (E(h)) in TM neurons was -35 +/- 9 (SD) mV. 4. The time constant of activation was well fit by a single exponential function and exhibited marked voltage dependence: at -90 mV, I(h) activated with a time constant of 823 +/- 35 ms, whereas at -130 mV, I(h) activated with a time constant of 280 +/- 65 ms. The time constant of deactivation of I(h) at -60 mV was 302 +/- 35 ms. 5. Raising the extracellular potassium concentration ([K+]o) to 10 mM shifted E(h) to a more depolarized value, while lowering the extracellular sodium concentration ([Na+]o) shifted E(h) in the negative direction. Altering the extracellular chloride concentration ([Cl-]o) had little effect on E(h). 6. Increasing [K+]o to 10 mM increased the amplitude of both I(h) and its underlying conductance g(h), while reducing [Na+]o caused a small reduction in the amplitude of I(h) with no measurable effect on g(h). 7. The time constant of activation of I(h) became shorter in raised [K+]o and longer in lowered [Na+]o. 8. Extracellularly applied cesium blocked I(h) in a voltage-dependent manner. Extracellular barium reduced I(h) but was less effective than cesium. 9. We conclude that I(h), carried by sodium and potassium ions, accounts for inward rectification of TM neurons. By increasing the whole-cell conductance during periods of prolonged hyperpolarization, I(h) may act as an ionic shunt, decreasing the efficacy of synaptic inputs. This effect would be most apparent during rapid-eye-movement sleep, when TM neurons fall silent.