title: Loss of T-type calcium current in sensory neurons of rats with neuropathic pain.
abstract: BACKGROUND
  Pathophysiology in the primary sensory neuron may contribute to chronic neuropathic pain. Ca channels play a central role in neuronal processes, and sensory neurons are rich in low-voltage-activated calcium channels (LVACCs). However, the physiologic function of these channels is unknown. Their possible role in rebound burst firing makes them a candidate for increased excitability after neuropathic injury.
  
  
  METHODS
  This study uses pharmacological methods to isolate LVACC in cells from the dorsal root ganglia of neuropathic and sham-operated rats, including the blockade of high-voltage-activated Ca channels with fluoride and selective toxins. LVACCs were examined with conventional whole cell patch clamp electrophysiology techniques.
  
  
  RESULTS
  After chronic constriction injury of the peripheral axon, LVACC was significantly reduced compared to sham rats as shown by a 60% reduction in peak current density and an 80% reduction in total calcium influx. A depolarizing shift in the voltage dependence of activation and an increase in the rate of deactivation and inactivation appear to cause this reduction of LVACC. Either Ni2+ or mibefradil, blockers of LVACC, applied in the bath to normal dorsal root ganglion cells during current clamp significantly and reversibly increased excitability.
  
  
  CONCLUSIONS
  These results suggest that loss of LVACC may contribute to decreased spike frequency adaptation and increased excitability after injury to sensory neurons. Through decreased Ca2+ influx, the cell becomes less stable and more likely to initiate or transmit bursts of action potentials. Consequently, modulation of Ca2+ currents at the dorsal root ganglion may be a potential method of therapeutic intervention.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Wisconsi 53226, USA. mccallum@mcw.edu
authors.forename: J Bruce
authors.initials: JB
authors.lastname: McCallum
authors.forename: Wai-Meng
authors.initials: WM
authors.lastname: Kwok
authors.forename: Michelle
authors.initials: M
authors.lastname: Mynlieff
authors.forename: Zeljko J
authors.initials: ZJ
authors.lastname: Bosnjak
authors.forename: Quinn H
authors.initials: QH
authors.lastname: Hogan
mesh_terms: D000465:Algorithms; D000818:Animals; D020747:Calcium Channels, T-Type / Q000502:physiology*; D002469:Cell Separation; D002908:Chronic Disease; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D010523:Peripheral Nervous System Diseases / Q000503:physiopathology*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology
chemical_list: D020747:Calcium Channels, T-Type