Delayed depolarization and slow sodium currents in cutaneous afferents.
1. Intraaxonal recordings were obtained in vitro from the sural nerve (SN), the muscle branch of the anterior tibial nerve (ATN), or the deafferented ATN (dATN) in 5- to 7-wk-old rats. Whole-nerve sucrose gap recordings were obtained from the SN and the ATN. This allowed study of cutaneous (SN), mixed motor and muscle afferent (ATN), and isolated muscle afferent (dATN) axons. 2. Application of the potassium channel blocking agent 4-aminopyridine (4-AP) to ATN or dATN resulted in a slight prolongation of the action potential. In contrast, a distinct delayed depolarization followed the axonal action potential in cutaneous afferents (SN) exposed to 4-AP. The delayed depolarization could be induced by a single whole-nerve stimulus or by injection of constant-current depolarizing pulses into individual axons. The delayed depolarization often gave rise to bursts of action potentials and was followed by a prominent afterhyperpolarization (AHP). 3. In paired-pulse experiments on single SN axons, the recovery time (half-amplitude of the action potential) was 3.06 +/- 1.82 (SE) ms (n = 12). After exposure to 4-AP the recovery time of the delayed depolarization was considerably longer (half-recovery time: 99.0 +/- 28.3 ms; n = 15) than that of the action potential (18.8 +/- 9.1 ms; n = 16). 4. Application of tetraethylammonium (TEA) to cutaneous or muscle afferents alone had little effect on single action potential waveform. However, TEA reduced the amplitude of the AHP elicited by a single stimulus in cutaneous afferent axons after exposure to 4-AP and resulted in repetitive spike discharge. 5. The delayed depolarization and spike burst activity induced by 4-AP in SN was present in Ca(2+)-free solutions containing 1 mM ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and was not blocked by Cd2+ (1.0 mM). 6. We obtained whole-cell patch-clamp recordings to study Na+ currents from either randomly selected dorsal root ganglion neurons or cutaneous afferent neurons identified by retrograde labeling with Fluoro-Gold. The majority of the randomly selected neurons had a singular kinetically fast Na+ current. In contrast, no identified cutaneous afferent neurons had a singular fast Na+ current. Rather, they had a combination of kinetically separable fast and slow currents or a singular relatively slow Na+ current.(ABSTRACT TRUNCATED AT 400 WORDS)
Honmou
O
O
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06510.
Utzschneider
D A
DA
Rizzo
M A
MA
Bowe
C M
CM
Waxman
S G
SG
Kocsis
J D
JD
D015761:4-Aminopyridine / Q000494:pharmacology; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009132:Muscles / Q000294:innervation; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000502:physiology; D010525:Peripheral Nerves / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000294:innervation*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013497:Sural Nerve / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013979:Tibial Nerve / Q000187:drug effects / Q000502:physiology
D015221:Potassium Channels; D015222:Sodium Channels; D015761:4-Aminopyridine