Carbon dioxide and pH effects in thermoregulatory hypothalamic neurons

The neural control of body temperature is regulated by the preoptic-anterior hypothalamus (POAH). POAH warming elicits heat loss responses (panting, sweating, peripheral vasodilation), while POAH cooling increases heat production (shivering, non-shivering thermogenesis). About 30% of POAH neurons are warm-sensitive, and their firing rates increase during brain warming. Neuronal models suggest that warm-sensitive neurons evoke heat loss responses. Studies suggest that increased CO2 and acidic pH impair heat loss. Accordingly, if endogenous factors like increased CO2 or acidic pH inhibit warm-sensitive neurons, this would explain the resulting hyperthermia due to reduced heat loss. These neuronal responses offer an explanation for heat stroke and other heat-related illnesses, where impaired heat loss is associated with acidosis. The majority of POAH neurons are considered temperature-insensitive, and their firing rates remain relatively constant during temperature changes. Neuronal models predict that heat production responses are inhibited by warm-sensitive neurons but excited by temperature-insensitive neurons. Whole-animal studies suggest that increases in hypothalamic guanosine 3',5 '-cyclic monophosphate (cyclic GMP) produce lower body temperatures. Therefore, if an endogenous substance (e.g., cyclic GMP) inhibits temperature-insensitive neurons, this could explain the resulting hypothermia due to reduced heat production. To test these predictions, the present experiments used extracellular and intracellular electrophysiological recordings to determine the effects of CO2, pH and cGMP on the firing rates of POAH temperature-sensitive and insensitiveneurons in rat hypothalamic tissue slices.;Increasing CO2 from 5% (normal) to 10% (hypercapnic) did not affect most POAH temperature-insensitive neurons; however, this inhibited the majority of warm-sensitive neurons. Hypercapnia reduced neuronal firing rates by: (1) decreasing the rate of depolarization of the pre-potential and (2) changing the action potential threshold to a more depolarized level. Lowering CO2 to 0% had the opposite effects on the pre-potential and threshold, and this tended to increase the firing rates. These CO 2 effects are due to pH changes, since acidosis produced neuronal effects that are similar to the hypercapic effects.;In the present study, increases in POAH intracellular cGMP tend to decrease firing rates, especially in temperature-insensitive neurons. Since neuronal models suggest that these neurons enhance heat production, the cGMP-induced inhibition may explain cGMP-induced hypothermia.