Brown fat is important in maintaining body temperature and preventing obesity in mammals through its adrenergically regulated thermogenic, energy wasting activity. Brown fat responds immediately to sympathetic nervous stimulation with large increases in metabolic rate and In the long-term with hypertrophy and an increased thermogenic capacity. Previous research has shown that the plasma membrane of brown fat cells contains potassium-selective ion channels that are activated during thermogenesis. The goal of the experiments proposed here is to characterize the properties of these potassium channels and to determine the role of potassium conductances in the thermogenic and mitogenic responses of brown fat cells. The proposed experiments will use acutely isolated and cultured brown fat cells from neonatal rats to 1) electrophysiologically and pharmacologically characterize ion channels in brown fat cells using patch voltage clamp techniques, 2) measure the effects of channel blockers on adrenergically stimulated heat production, 3) determine the effects of channel blockers on brown fat cell proliferation, and 4) examine the role of the surface membrane in affecting internal calcium ion concentrations using fluorescent imaging methods. The results of these experiments will provide information on the cellular mechanisms of brown fat thermogenesis and its 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 potassium channels in metabolic responses that may be important in many energetically active cells.
| Lee, S C; Hamilton, J S; Trammell, T et al. (1994) Adrenergic modulation of intracellular pH in isolated brown fat cells from hamster and rat. Am J Physiol 267:C349-56 |
| Lee, S C; Nuccitelli, R; Pappone, P A (1993) Adrenergically activated Ca2+ increases in brown fat cells: effects of Ca2+, K+, and K channel block. Am J Physiol 264:C217-28 |
| Pappone, P A; Ortiz-Miranda, S I (1993) Blockers of voltage-gated K channels inhibit proliferation of cultured brown fat cells. Am J Physiol 264:C1014-9 |
| Pappone, P A; Lucero, M T (1992) Potassium channel block does not affect metabolic responses of brown fat cells. Am J Physiol 262:C678-81 |
