The effects of QX-314 on medullary respiratory neurones |
| |
| Authors: | Steven Mifflin Diethelm W Richter |
| |
| Institution: | 1. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3010, Australia;2. Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;3. Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, USA;4. Department of Physiology, University of Melbourne, Australia;5. Department of Biomedical and Neuromotor Science (DIBINEM), University of Bologna, Bologna, Italy;1. Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Nørre Allé 14, 2200, Copenhagen, Denmark;2. Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genomics, Faculty of Health and Medical Sciences, University of Copenhagen, Nørre Allé 14, 2200, Copenhagen, Denmark;3. Department of Neuroscience, University of Copenhagen, Nørre Allé 14, 2200, Copenhagen, Denmark;4. Department of Biochemistry, UT Southwestern Medical Center at Dallas, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA;5. Division of Hypothalamic Research and Department of Internal Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA;1. Department of Clinical Sciences, Division of Experimental Vascular Research, Lund University, BMC A13, Sölvegatan 17, SE-22184 Lund, Sweden;2. Department of Pain and Migraine Research, Merck Research Laboratories, West Point, PA, USA;3. Department of Clinical Experimental Research, Glostrup Research Institute, Glostrup Hospital, Glostrup, Denmark;4. Department of Imaging, Merck Research Laboratories, West Point, PA, USA;1. Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, India;2. Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia;3. School of Pharmacy, Griffith University, Gold Coast, Australia |
| |
| Abstract: | The synaptic and current-evoked responses of respiratory neurones located in the nucleus of the tractus solitarius, the para- and retroambigual regions and the nucleus ambiguus, were examined after voltage-dependent sodium currents were blocked by intracellular application of the quaternary lidocaine derivative QX-314. (1) QX-314 abolished orthodromically and antidromically evoked action potential discharge. Only antidromic action potentials recovered during negative DC current injection. (2) QX-314 did not alter the amplitude or duration of small and short excitatory and inhibitory postsynaptic potentials evoked by vagus or superior laryngeal nerve stimulation. Larger and longer waves of spontaneous membrane depolarizations, however, were slightly diminished. (3) The repetitive discharge evoked by depolarizing current pulses was blocked by QX-314. Positive current pulses produced less membrane depolarization than under control and often evoked only a single action potential at the beginning of the pulse, indicating that QX-314 interferes with the processes responsible for repetitive firing. (4) When fast spike discharges were completely blocked, positive current pulses occasionally evoked depolarizing 'spikes' and potentials which were followed by a hyperpolarization. We conclude that a noninactivating sodium inward current and calcium currents contribute to the electroresponsiveness of respiratory neurones. |
| |
| Keywords: | Respiratory neuron Repetitive discharge Calcium current QX-314 |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
