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

• Published in: Journal of applied physiology (1985) 2000-06, Vol.88 (6), p.2319-2329
• Main Authors: Mazza, Emilio, Jr, Edelman, Norman H, Neubauer, Judith A
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn - physiology; Biological and medical sciences; Cells, Cultured; Dose-Response Relationship, Drug; Electric Impedance; Electrophysiology; Fundamental and applied biological sciences. Psychology; Hypoxia - physiopathology; Medulla Oblongata - drug effects; Medulla Oblongata - pathology; Medulla Oblongata - physiopathology; Membrane Potentials - drug effects; Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration; Neurons - drug effects; Neurons - physiology; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Sodium Cyanide - pharmacology; Vertebrates: nervous system and sense organs
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/jappl.2000.88.6.2319

1  Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903-0019; and 2  Departments of Physiology and Biophysics and of Medicine, State University of New York at Stony Brook, Stony Brook, New York 11794-8661 Neurons within cardiorespiratory regions of the rostral ventrolateral medulla (RVLM) have been shown to be excited by local hypoxia. To determine the electrophysiological properties of these excitatory responses to hypoxia, we developed a primary dissociated cell culture system to examine the intrinsic response of RVLM neurons to hypoxia. Neonatal rat neurons plated on medullary astrocyte monolayers were studied using the whole cell perforated patch-clamp technique. Sodium cyanide (NaCN, 0.5-10 mM) was used, and membrane potential ( V m ), firing frequency, and input resistance were examined. In 11 of 19 neurons, NaCN produced a V m depolarization, an increase in firing 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 hyperpolarized V m . In 8 of 19 neurons, NaCN produced a V m hyperpolarization, decrease in firing frequency, and variable changes in input resistance. The V m hyperpolarization exhibited an all-or-none dose response and was independent of baseline V m . These differential responses to NaCN were retained after synaptic blockade with low Ca 2+ -high Mg 2+ or TTX. Thus hypoxic excitation 1 ) is maintained in cell culture, 2 ) is an intrinsic response, and 3 ) is likely due to the increase in a cation current. These hypoxia-excited neurons are likely candidates to function as central oxygen sensors. respiratory; sympathetic; sodium cyanide; whole cell perforated patch clamp