Role of hyperpolarization‐activated currents in hypothalamic neuronal thermosensitivity

Abstract

The thermoregulatory preoptic-anterior hypothalamus (POAH) contains both temperature sensitive and insensitive neurons. Our previous studies predict that neuronal warm-sensitivity is due to thermosensitive pacemaker currents that include both the inactivation of transient outward K+ currents and the activation of Ih (cation currents activated by hyperpolarization). The latter include inward currents through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Our recent modeling study (Wechselberger et al, Am. J. Physiol. 2006) predicts that HCN channels contribute to neuronal warm-sensitivity, while K+ leak channels contribute to temperature insensitivity. Since POAH neurons show differences in their HCN immunoreactivity, the present study tested the models’ predictions by measuring Ih in different types of POAH neurons recorded in rat hypothalamic tissue slices. During current-clamp recordings, each neuron was characterized by its spontaneous activity at 36°C and by its firing rate thermosensitivity (impulses/sec/°C) when the tissue slice was warmed and cooled. Voltage-clamp recordings measured Ih and the effects of temperature on this current. In support of the models’ predictions, our experiments to date indicate that Ih is often associated with neurons displaying pacemaker activity and warm-sensitivity. [Supported by NIH grants NS14644 and NS045758]