The Journal of Neurophysiology Vol. 77 No. 6 June 1997, pp. 3284-3296
Copyright ©1997 The American Physiological Society

Two Parallel Signaling Pathways Couple 5HT_1A Receptors to N- and L-Type Calcium Channels in C-Like Rat Dorsal Root Ganglion Cells

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 Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ channels by two different signaling pathways in type 1 DRG cells. The inhibition of Ca²⁺ 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 Ca²⁺ channels selectively reduced the kinetic slowing and its reversal by prepulses. Chelation of intracellular Ca²⁺ or blockade of L-type Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ 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 Ca²⁺, which couples to L channels and actuates steady state inhibition.

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