Contribution of calcium channel subtypes to the intracellular calcium signal in sensory neurons: the effect of injury.
BACKGROUND
Although the activation-induced intracellular Ca signal is disrupted by sensory neuron injury, the contribution of specific Ca channel subtypes is unknown.


METHODS
Transients in dissociated rat dorsal root ganglion neurons were recorded using fura-2 microfluorometry. Neurons from control rats and from neuropathic animals after spinal nerve ligation were activated either by elevated bath K or by field stimulation. Transients were compared before and after application of selective blockers of voltage-activated Ca channel subtypes.


RESULTS
Transient amplitude and area were decreased by blockade of the L-type channel, particularly during sustained K stimulation. Significant contributions to the Ca transient are attributable to the N-, P/Q-, and R-type channels, especially in small neurons. Results for T-type blockade varied widely between cells. After injury, transients lost sensitivity to N-type and R-type blockers in axotomized small neurons, whereas adjacent small neurons showed decreased responses to blockers of R-type channels. Axotomized large neurons were less sensitive to blockade of N- and P/Q-type channels. After injury, neurons adjacent to axotomy show decreased sensitivity of K-induced transients to L-type blockade but increased sensitivity during field stimulation.


CONCLUSIONS
All high-voltage-activated Ca current subtypes contribute to Ca transients in sensory neurons, although the L-type channel contributes predominantly during prolonged activation. Injury shifts the relative contribution of various Ca channel subtypes to the intracellular Ca transient induced by neuronal activation. Because this effect is cell-size specific, selective therapies might potentially be devised to differentially alter excitability of nociceptive and low-threshold sensory neurons.
Fuchs
Andreas
A
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Rigaud
Marcel
M
Sarantopoulos
Constantine D
CD
Filip
Patrick
P
Hogan
Quinn H
QH
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002469:Cell Separation; D048429:Cell Size; D002478:Cells, Cultured; D003592:Cytophotometry; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D006930:Hyperalgesia / Q000503:physiopathology / Q000523:psychology; D008026:Ligation; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D059348:Peripheral Nerve Injuries; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000293:injuries*; D014855:Wallerian Degeneration / Q000503:physiopathology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D015221:Potassium Channels