作者: Sheana E Desson , Alastair Victor Ferguson , None
DOI: 10.1113/JPHYSIOL.2003.041210
关键词:
摘要: The circumventricular organs (CVOs) are ideal locations at which circulating pyrogens may act to communicate with the CNS during an immune challenge. Their dense vasculature and fenestrated capillaries allow direct access of these tissue without impediment blood-brain barrier (BBB). One such CVO, subfornical organ (SFO), has been implicated as a site endogenous pyrogen interleukin 1β (IL-1β) acts initiate febrile response. This study was designed determine response rat SFO neurons IL-1β (1 nM 100 fM) using whole-cell current-clamp voltage-clamp techniques. We found that physiological (subseptic) concentrations pM, 500 fM, induced transient depolarization in accompanied by significant increase spike frequency. In contrast, pharmacological (septic) nM) evoked sustained hyperpolarization. While depolarizations were abolished treatment cells IL-1 receptor antagonist (IL-1ra), hyperpolarizations still observed. Voltage-clamp analysis revealed majority (85 %) responding (29 34 cells) exhibited electrophysiological profile characterized dominant delayed rectifier potassium current (DIK), conductance we also be reduced 84.4 ± 3.3 % control bath application IL-1β. addition, slow voltage ramps demonstrated activates non-selective cationic (INSC) reversal potential −38.8 1.8 mV. These studies identify cellular mechanisms through can influence excitability and, consequence actions, exogenous pyrogens.