Acute temperature sensitivity in optic nerve axons explained by an electrogenic membrane potential.
Classical work in squid axon reports resting membrane potential is independent of temperature, but our findings suggest that this is not the case for axons in mammalian optic nerve. Refractory period duration changes over 10 times between 37 °C and room temperature, and afterpotential polarity is also acutely temperature sensitive, inconsistent with changes in temperature impacting nerve function only through altered rates of ion channel gating kinetics. Our evidence suggests that the membrane potential is enhanced by warming, an effect reduced by exposure to ouabain. The temperature dependence can be explained if axonal Na(+)/K(+) ATPase continuously expels Na(+) ions that enter axons largely electroneutrally, thereby adding a substantial electrogenic component to the membrane potential. Block of the Na(+) transporter NKCC1 with bumetanide increases refractoriness, like depolarization, indicating that this is a probable route by which Na(+) enters, raising the expectation that the rate of electroneutral Na(+) influx increases with temperature and suggesting a temperature-dependent transmembrane Na(+) cycle that contributes to membrane potential.
Neuroscience and Trauma Centre, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, 4 Newark Street, London, E12AT, UK.
Tom A
TA
Coates
Neuroscience and Trauma Centre, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, 4 Newark Street, London, E12AT, UK.
Oscar
O
Woolnough
Neuroscience and Trauma Centre, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, 4 Newark Street, London, E12AT, UK.
Joseph M
JM
Masters
Neuroscience and Trauma Centre, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, 4 Newark Street, London, E12AT, UK.
Gulsum
G
Asadova
Neuroscience and Trauma Centre, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, 4 Newark Street, London, E12AT, UK.
Charmilie
C
Chandrakumar
Neuroscience and Trauma Centre, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, 4 Newark Street, London, E12AT, UK. m.d.baker@qmul.ac.uk.
Mark D
MD
Baker
D000818:Animals; D001369:Axons / Q000502:physiology*; D002034:Bumetanide / Q000494:pharmacology; D055724:Electrophysiological Phenomena / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009900:Optic Nerve / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012032:Refractory Period, Electrophysiological / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism; D013696:Temperature
D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; C578879:Slc12a2 protein, rat; D064506:Solute Carrier Family 12, Member 2; D002034:Bumetanide; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase
Bumetanide; Membrane potential; NKCC1; Na+/K+-ATPase; Optic nerve; Ouabain; Recovery cycle