Hypoxic excitation in neurons cultured from the rostral ventrolateral medulla of the neonatal rat

Neurons within cardiorespiratory regions of the rostral ventrolateral medul la (RVLM) have been shown to be excited by local hypoxia. To determine the electrophysiological properties of these excitatory responses to hypoxia, w e developed a primary dissociated cell culture system to examine the intrin sic response of RVLM neurons to hypoxia. Neonatal rat neurons plated on med ullary astrocyte monolayers were studied using the whole cell perforated pa tch-clamp technique. Sodium cyanide (NaCN, 0.5-10 mM) was used, and membran e potential (V-m), firing frequency, and input resistance were examined. In 11 of 19 neurons, NaCN produced a V-m depolarization, an increase in firin g frequency, and a decrease in input resistance, suggesting the opening of a cation channel. The hypoxic depolarization had a linear dose response and was dependent on baseline V-m, with a greater response at more hyperpolari zed V-m. In 8 of 19 neurons, NaCN produced a V-m hyperpolarization, decreas e in firing frequency and variable changes in input resistance. The V-m hyp erpolarization exhibited an all-or-none dose response and was independent o f baseline V-m. These differential responses to NaCN were retained after sy naptic blockade with low Ca2+-high Mg2+ or TTX. Thus hypoxic excitation 1) is maintained in cell culture, 2) is an intrinsic response, and 3) is likel y due to the increase in a cation current. These hypoxia-excited neurons ar e likely candidates to function as central oxygen sensors.