Ligature-induced injury in peripheral nerve: electrophysiological observations on changes in action potential characteristics following blockade of potassium conductance.
The effects of the potassium channel blocking agent 4-aminopyridine (4-AP) on action potential properties were studied in chronically injured rat sciatic nerves. In normal, mature myelinated fibers, application of 4-AP does not lead to any significant change in action potential waveform or firing pattern in response to single stimuli. In contrast, application of 4-AP to nerves injured by the placement of loose ligatures results in the appearance of late rippled components in the compound action potential. This alteration in waveform is present at the injury site, but not at nerve segments proximal or distal to this region. Paired stimulation experiments demonstrate that this oscillation of the whole nerve response reflects repetitive firing in response to single stimuli following application of 4-AP. Intra-axonal recording following 4-AP application demonstrates bursts of action potentials, with several spikes of reduced amplitude arising from a depolarizing potential following the initial spike. Refractory period for the late spike is greater than that of the primary action potential. These results demonstrate that potassium channels are present and functional in chronically injured nerves, where blockage of these channels results in repetitive firing in response to single stimuli.
Waxman
S G
SG
Kocsis
J D
JD
Eng
D L
DL
D015761:4-Aminopyridine; D000200:Action Potentials / Q000187:drug effects; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000502:physiology; D004594:Electrophysiology; D007473:Ion Channels / Q000378:metabolism; D009186:Myelin Sheath / Q000502:physiology; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000187:drug effects / Q000502:physiology; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000631:Aminopyridines; D007473:Ion Channels; D015761:4-Aminopyridine; D011188:Potassium