Brown fat is important for maintaining body temperature and energy balance in mammals through its thermogenic, energy wasting activity, and is currently being explored as a target for antiobesity therapies. Brown fat cells respond rapidly to sympathetic adrenergic stimulation with large increases in metabolic rate, and sustained sympathetic activation caused hypertrophy and increased thermogenic capacity of the tissue. Hormonal stimulation of brown fact activates both hyperpolarizing and depolarizing membrane conductances. The experiments in this proposal are designed to determine the physiological roles of depolarizing conductances in brown fat. Specifically the experiments will use acutely isolated and cultured brown fat cell from neonatal rats to 1) electrophysiologically and pharmacologically characterize the depolarizing conductances and determine how their activity is regulated using patch voltage clamp techniques, and 2) determine the effects of depolarizing conductances on thermogenesis, mitogenesis, and intracellular ionic signalling systems using calorimetry, cell culture, and fluorescent indicator photometry techniques. The results of these experiments will provide information on the cellular mechanisms of hormone responses in brown fat cells and their regulation and modulation, and so will be relevant to the medically important problem of obesity. More generally, these results will give insight into the functions of membrane ion fluxes in metabolic and hormonal responses that may be important in may energetically active cells.
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