Date of Award
Doctor of Philosophy
Veterinary Physiology and Pharmacology
Voltage-activated Ca[superscript]2+ currents in immature rat spinal dorsal horn neurons and their modulation by substance P (SP) and calcitonin gene-related peptide (CGRP) have been investigated by using single-electrode voltage-clamp technique in the transverse spinal cord slice preparation;Using experimental conditions that minimized voltage-dependent Na[superscript]+ and K[superscript]+ currents, we distinguished low- and high-voltage-activated Ca[superscript]2+ currents on the basis of their voltage dependence and sensitivity to the Ca[superscript]2+ channel agonist and antagonist drugs. The low-voltage-activated (LVA) transient Ca[superscript]2+ current is evoked with weak depolarizing voltage commands at potentials positive to -70 mV and reaches the peak value between -40 and -30 mV. Inactivation is complete at potentials in the range of -60 to -50 mV. The transient component of the high-voltage-activated (HVA) Ca[superscript]2+ current activates at membrane potentials close to -40 mV and decays with time constants ranging from 100-600 ms. The sustained component of the HVA Ca[superscript]2+ current activates at potentials positive to -40 mV and exhibits little inactivation during 0.3-0.5s depolarizing commands. Bay K 8644 enhanced selectively the sustained component of the HVA Ca[superscript]2+ current, whereas nifedipine reduced this component of Ca[superscript]2+ current. Cd[superscript]2+ and Co[superscript]2+ ions markedly reduced both the transient and sustained components of the HVA Ca[superscript]2+ current. Nickel ions reduced the LVA transient Ca[superscript]2+ current;Bath application of CGRP elicited hyperpolarization in both small and large DRG neurons that was associated with an increase in membrane input resistance. However, some large DRG neurons were depolarized by CGRP. In addition, CGRP produced an increase in the amplitude and the duration of the Ca[superscript]2+ spike and increased the voltage-dependent Ca[superscript]2+ current by enhancing both the transient and the sustained components of high-threshold Ca[superscript]2+ current;CGRP depolarized about one-third of the dorsal horn neurons and increased their input resistance and excitability. CGRP increased the amplitude of the fast excitatory postsynaptic potentials recorded in dorsal horn neurons in response to electrical stimulation of a lumbar dorsal root. The increase in Ca[superscript]2+ current in DRG neurons is likely to be responsible for the facilitation of excitatory synaptic transmission;SP enhanced a low-threshold, transient Ca[superscript]2+ current in rat dorsal horn neurons. This effect may be responsible for the increase in excitability produced by SP.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/
Pan Dong Ryu
Ryu, Pan Dong, "Voltage sensitive Ca2+ conductances mediating modulatory effects of neuropeptides in rat spinal dorsal horn neurons " (1989). Retrospective Theses and Dissertations. 9236.