The pH dependence of late sodium current in large sensory neurons.
The effects of altering extracellular pH on late Na+ currents were investigated in large dorsal root ganglion neurons from rats (100-300 g), using patch-clamp techniques. The late current amplitude was steeply dependent upon pH over a range which included normal physiological values: raising the pH from 7.3 to 8.3 approximately doubled the amplitude. Whole-cell late currents 60 ms after depolarization to - 30 mV were blocked with an apparent pKa of 6.96. The pH-dependent changes in current amplitude could not be accounted for by the effects of altered surface charge. In recordings of unitary Na+ currents from outside-out membrane patches, acidification promoted channel opening to a reduced conductance level, near one-half of its maximal value. Acidification to pH < 6.0 also changed the kinetics of the current recruited with the lowest threshold from non-inactivating to inactivating, with the elimination of late openings. We conclude that lowering pH from an initial alkaline or neutral value blocks late Na+ current by reducing the number of contributing channels while also reducing the single channel conductance. The pH dependence of late Na+ current helps to explain clinically relevant changes in neuronal excitability in response to small (i.e. < 1 unit) perturbations in extracellular pH.
Baker
M D
MD
Sobell Department of Neurophysiology, Institute of Neurology, London, UK.
Bostock
H
H
D000818:Animals; D048429:Cell Size; D002478:Cells, Cultured; D004553:Electric Conductivity; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009475:Neurons, Afferent / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000502:physiology*; D015222:Sodium Channels / Q000378:metabolism; D013997:Time Factors
D015222:Sodium Channels; D006859:Hydrogen; D012964:Sodium