gaba increases electrical excitability in a subset of human unmyelinated peripheral axonsgaba电兴奋性增加人类无髓鞘的周围轴突的一个子集.pdfVIP

GABA Increases Electrical Excitability in a Subset of Human Unmyelinated Peripheral Axons 1 1 2 1 Richard W. Carr *, Ruth Sittl , Johannes Fleckenstein , Peter Grafe 1 Institute of Physiology, Ludwig-Maximilians University, Munich, Germany, 2 Department of Anaesthesiology, Ludwig-Maximilians University, Munich, Germany Abstract Background: A proportion of small diameter primary sensory neurones innervating human skin are chemosensitive. They respond in a receptor dependent manner to chemical mediators of inflammation as well as naturally occurring algogens, thermogens and pruritogens. The neurotransmitter GABA is interesting in this respect because in animal models of neuropathic pain GABA pre-synaptically regulates nociceptive input to the spinal cord. However, the effect of GABA on human peripheral unmyelinated axons has not been established. Methodology/Principal Findings: Electrical stimulation was used to assess the effect of GABA on the electrical excitability of unmyelinated axons in isolated fascicles of human sural nerve. GABA (0.1–100 mM) increased electrical excitability in a subset (ca. 40%) of C-fibres in human sural nerve fascicles suggesting that axonal GABA sensitivity is selectively restricted to a sub-population of human unmyelinated axons. The effects of GABA were mediated by GABAA receptors, being mimicked by bath application of the GABAA agonist muscimol (0.1–30 mM) while the GABAB agonist baclofen (10–30 mM) was without effect. Increases in excitability produced by GABA (10–30 mM) were blocked by the GABAA antagonists gabazine (10– 20 mM), bicuculline (10–20 mM) and picrotoxin (10–20 mM). Conclusions/Significance: Functional GABAA receptors are pres