Naslov
Failure of action potential propagation in sensory neurons : mechanisms and loss of afferent filtering in C-type units after painful nerve injury

Autori
Gemes, Geza ; Koopmeiners, Andrew ; Koopmeiners, Andrew ; Rigaud, Marcel ; Lirk, Philipp ; Sapunar, Damir ; Bangaru, Madhavi Latha ; Vilceanu, Daniel ; Garrison, Sheldon R. ; Ljubković, Marko ; Mueller, Samantha J. ; Stucky, Cheryl L ; Hogan, Quinn H.

Izvornik
Journal of physiology (London) (0022-3751) 591 (2013), 4; 1111-1131

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
dorsal-root ganglion; current i-h; rapidly adapting mechanoreceptors; hippocampal pyramidal neurons; human glabrous skin; k+ channels; neuropathic pain; purkinje neurons; calcium current; afterhyperpolarizing current
(DORSAL-ROOT GANGLION; CURRENT I-H; RAPIDLY ADAPTING MECHANORECEPTORS; HIPPOCAMPAL PYRAMIDAL NEURONS; HUMAN GLABROUS SKIN; K+ CHANNELS; NEUROPATHIC PAIN; PURKINJE NEURONS; CALCIUM CURRENT; AFTERHYPERPOLARIZING CURRENTdorsal-root ganglion; current i-h; rapidly adapting mechanoreceptors; hippocampal pyramidal neurons; human glabrous skin; k+ channels; neuropathic pain; purkinje neurons; calcium current; afterhyperpolarizing current)

Sažetak
Key points center dot The peripheral terminals of sensory neurons encode physical and chemical signals into trains of action potentials (APs) and transmit these trains to the CNS. center dot Although modulation of this process is thought to predominantly reside at synapses, there are also indications that AP trains are incompletely propagated past points at which axons branch. One such site is the T-junction, where the single sensory neuron axon branches into peripheral and central processes. center dot In recordings from sensory neurons of dorsal root ganglia excised from adult rats, we identified use-dependent failure of AP propagation between the peripheral and central processes that results in filtering of rapid AP trains, especially in C-type neurons. center dot Propagation failure was regulated by membrane input resistance and Ca2+-sensitive K+ and Cl currents. Following peripheral nerve injury, T-junction filtering is reduced in C-type neurons, which may possibly contribute to pain generation. Abstract The T-junction of sensory neurons in the dorsal root ganglion (DRG) is a potential impediment to action potential (AP) propagation towards the CNS. Using intracellular recordings from rat DRG neuronal somata during stimulation of the dorsal root, we determined that the maximal rate at which all of 20 APs in a train could successfully transit the T-junction (following frequency) was lowest in C-type units, followed by A-type units with inflected descending limbs of the AP, and highest in A-type units without inflections. In C-type units, following frequency was slower than the rate at which AP trains could be produced in either dorsal root axonal segments or in the soma alone, indicating that the T-junction is a site that acts as a low- pass filter for AP propagation. Following frequency was slower for a train of 20 APs than for two, indicating that a cumulative process leads to propagation failure. Propagation failure was accompanied by diminished somatic membrane input resistance, and was enhanced when Ca2+- sensitive K+ currents were augmented or when Ca2+- sensitive Cl currents were blocked. After peripheral nerve injury, following frequencies were increased in axotomized C-type neurons and decreased in axotomized non-inflected A-type neurons. These findings reveal that the T-junction in sensory neurons is a regulator of afferent impulse traffic. Diminished filtering of AP trains at the T-junction of C-type neurons with axotomized peripheral processes could enhance the transmission of activity that is ectopically triggered in a neuroma or the neuronal soma, possibly contributing to pain generation.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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