Two Parallel Signaling Pathways Couple 5HT1A Receptors to N- and L-Type Calcium Channels in C-Like Rat Dorsal Root Ganglion Cells

• Published in: Journal of neurophysiology Vol. 77; no. 6; pp. 3284 - 3296
• Main Authors: Cardenas, Carla G, Mar, Lucinda P. Del, Scroggs, Reese S
• Format: Journal Article
• Language: English
• Published: United States Am Phys Soc 01.06.1997
• Subjects: Animals; Calcium Channels - classification; Calcium Channels - physiology; Culture Techniques; Ganglia, Spinal - physiology; Male; Membrane Potentials - physiology; Nerve Fibers - physiology; Neural Inhibition - physiology; Nociceptors - physiology; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Receptors, Serotonin - physiology; Receptors, Serotonin, 5-HT1; Signal Transduction - physiology
• ISSN: 0022-3077; 1522-1598

Carla G. Cardenas , Lucinda P. Del Mar , and Reese S. Scroggs Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee, Memphis, Tennessee 38163 Cardenas, Carla G., Lucinda P. Del Mar, and Reese S. Scroggs. Two parallel signaling pathways couple 5HT 1A receptors to N- and L-type calcium channels in C-like rat dorsal root ganglion cells. J. Neurophysiol. 77: 3284-3296, 1997. The coupling of serotonin receptors to Ca 2+ channels was studied in a subpopulation of acutely isolated rat dorsal root ganglion (DRG) cell bodies (type 1 DRG cells), which have membrane properties similar to C-type nociceptive sensory neurons. In these cells, serotonin (5HT) inhibited high-threshold Ca 2+ channel current and decreased action potential duration. The inhibitory effects of 5HT and the 5HT 1A agonist 8-OH-DPAT were shown to be antagonized by the 5HT 1A antagonists spiperone and pindolol, respectively, indicating involvement of a 5HT 1A receptor. Several observations suggest that 5HT 1A receptors couple to N- and L-type Ca 2+ channels by two different signaling pathways in type 1 DRG cells. The inhibition of Ca 2+ channel currents produced by 10 µM 5HT occurred in two phases, an initial slowing of current activation rate (kinetic slowing), which was complete within 10 s, and a simultaneous reduction in steady state current amplitude (steady state inhibition), which peaked in ~1 min. The kinetic slowing, but not steady state inhibition, was reversed by a positive prepulse to +70 mV (prepulse). Blockade of N-type Ca 2+ channels selectively reduced the kinetic slowing and its reversal by prepulses. Chelation of intracellular Ca 2+ or blockade of L-type Ca 2+ channels selectively reduced the steady state inhibition. Recordings using the cell-attached patch configuration suggest that steady state inhibition required a component that was diffusible in the cytosol, while kinetic slowing occurred via a membrane delimited pathway. The application of 5HT to the cell body outside the patch pipette reduced macroscopic Ca 2+ channel currents in 33% of small-diameter DRG cells tested, indicating the participation of a cytosolic diffusible component. Application of 5HT (a membrane impermeant compound) outside the patch pipette produced steady state inhibition only, whereas similar application of membrane permeant 5HT 1A agonists, 8-OH-DPAT or 5-methoxy- N , N -dimethyl-tryptamine, produced kinetic slowing and steady state inhibition. Together these data suggest that 5HT 1A receptors couple negatively to Ca 2+ channels via two pathways: a membrane-delimited pathway that couples to N-channels and actuates voltage-sensitive kinetic slowing and a pathway dependent on a cytosolic diffusible component and free intracellular Ca 2+ , which couples to L channels and actuates steady state inhibition.