DELAYED DEPOLARIZATION AND SLOW SODIUM CURRENTS IN CUTANEOUS AFFERENTS
DELAYED DEPOLARIZATION AND SLOW SODIUM CURRENTS IN CUTANEOUS AFFERENTS
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DOI：
10.1152/jn.1994.71.5.1627
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发表时间：
1994-05-01
影响因子：
2.5
通讯作者：
KOCSIS, JD
中科院分区：
文献类型：
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作者：
HONMOU, O;UTZSCHNEIDER, DA;KOCSIS, JD
1.取5~7周龄大鼠的腓肠神经(SN)、胫前神经的肌支(ATN)或传出的ATN(DATN)进行轴突内记录。从SN和ATN获得全神经蔗糖间隙记录。这使得对皮肤(SN)、混合运动和肌肉传入(ATN)和单独的肌肉传入(DATN)轴突的研究成为可能。将钾通道阻断剂4-氨基吡啶(4-AP)应用于ATN或dATN，可使动作电位轻微延长。相反，暴露于4-AP的皮肤传入神经(SN)的轴突动作电位出现明显的延迟除极。延迟的去极化可以由单一的全神经刺激或通过向单个轴突注入恒流去极化脉冲来诱导。延迟除极常引起动作电位爆发，随后出现明显的后超极化(AHP)。在单个SN轴突的双脉冲实验中，恢复时间(动作电位的半幅)为3.06±1.82(SE)ms(n=12)。暴露于4-AP后，延迟除极的恢复时间(半恢复时间：99.0±28.3ms；n=15)明显长于动作电位的恢复时间(18.8±9.1ms；n=16)。皮肤或肌肉传入单独应用四乙基铵(TEA)对单个动作电位波形影响不大。但是，TEA可降低4-AP引起的单次刺激引起的皮肤传入轴突AHP的幅度，并导致重复的棘波放电。在含1 mM乙二醇双(β-氨基乙醚)-N，N，N‘N’-四乙酸的无钙溶液中，4-AP诱发的SN延迟去极化和峰爆发活动不被Cd~(2+)(1.0 mM)阻断。我们获得了全细胞膜片钳记录，以研究随机选择的背根节神经元或皮肤传入神经元的Na+电流。大多数随机选择的神经元都有一种奇异的动态快Na+电流。相比之下，没有已鉴定的皮肤传入神经元具有单一的快Na+电流。相反，它们具有动力学上可分离的快电流和慢电流的组合，或者是相对较慢的单一的Na+电流。这些结果表明，有髓皮肤和肌肉传入轴突对阻断4-AP敏感的K+通道的敏感性不同。皮肤传入轴突在动作电位后产生显著的去极化电位，这在肌肉传入或运动性轴突中不存在。我们认为，皮肤传入轴突具有运动性缓慢的Na+通道，这是肌肉传入和传出纤维中不存在的，其激活是延迟去极化和多个棘波放电的基础。结果表明，有髓皮肤和肌肉传入轴突及其胞体的Na+通道组织存在差异。
1. Intraaxonal recordings were obtained in vitro from the sural nerve ( SN), the muscle branch of the anterior tibial nerve ( ATN), or the deefferented 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 he 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 Ca2+-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.7. These results demonstrate a difference in the sensitivity of myelinated cutaneous and muscle afferent axons to blockade of a 4-AP-sensitive K+ channel. Cutaneous afferent axons give rise to a prominent depolarizing potential after the action potential, which is not present in the muscle afferent or motor axons. We propose that cutaneous afferent axons have kinetically slow Na+ channels not present in muscle afferent and efferent fibers, whose activation underlies the delayed depolarization and multiple spike discharge. The results indicate a difference in the Na+ channel organization of myelinated cutaneous versus muscle afferent axons and their cell bodies.