Variation in serotonergic inhibition of calcium channel currents in four types of rat sensory neurons differentiated by membrane properties

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Abstract
1. Rat dorsal root ganglion (DRG) cell bodies were screened according to action potential (AP) duration, capsaicin sensitivity, expression of IH, IA, and N-, L-, and T-type Ca2+ channel currents. AP duration was measured at half of total amplitude at a membrane potential of -60 mV. Sensitivity to capsaicin was defined as production of an inward current at a holding potential (HP) of -60 mV by 1 microM capsaicin. IH was evoked by a 787-ms hyperpolarization to -110 mV from an HP of -60 mV. IA was evoked by repolarization to -60 mV after a 787-ms hyperpolarization to -110 mV. High-threshold Ca2+ channel current was evoked by a depolarization to -10 or 0 mV from an HP of -60 mV, and L- and N-type Ca2+ channel current was fractionated using selective Ca2+ channel blockers (nimodipine and omega-conotoxin GVIA). T-type Ca2+ channel current was evoked by a depolarization to -40 mV from an HP of -90 mV. Ninety-seven of the 116 DRG cells studied fit closely into one of four categories based on expression of the above characteristics. These four categories, referred to as types 1-4, are described below. 2. Type 1 DRG cells (soma diameter 24.6 +/- 0.5 microns, mean +/- SE; n = 34) had long-duration APs (average = 9.8 ms) with a prominent shoulder on the falling limb and were capsaicin sensitive. Significant IH or IA was not expressed. High-threshold Ca2+ channel current was on average 28% omega-conotoxin GVIA sensitive (N-type) and 46% nimodipine sensitive (L-type); 26% was resistant to both blockers (resistant). T-type Ca2+ channel currents averaged 245 pA. 3. Type 2 DRG cells (soma diameter 25.2 +/- 0.9 microns, n = 19) had short-duration APs (average = 2.9 ms) with a small shoulder on the falling limb and were capsaicin sensitive. IH was negligible but IA averaged 184 pA. High-threshold Ca2+ channel current averaged 42% N-type, 23% L-type, and 35% resistant. T-type Ca2+ channel currents averaged 47 pA. 4. Type 3 DRG cells (soma diameter 18.6 +/- 0.8 microns, n = 21) had short-duration APs (average = 1.8 ms) and were insensitive to capsaicin. IA was not expressed but IH averaged 147 pA. High-threshold Ca2+ channel current averaged 27% N-type, 44% L-type, and 29% resistant. T-type Ca2+ channel currents averaged 306 pA. 5. Type 4 DRG cells (soma diameter 33.9 +/- 0.4 microns, n = 23) had short-duration APs (average = 1.1 ms) and were capsaicin insensitive. IA was not expressed but IH averaged 810 pA. High-threshold Ca2+ channel current was 16% N-type, 4% L-type, and 80% resistant. T-type Ca2+ channel currents averaged 4,031 pA. 6. There was a large variation in the inhibition of high-threshold Ca2+ channel currents by serotonin (5-HT) and (+)8-OH-DPAT in type 1 DRG cells versus types 2-4. On average, 5-HT (10 microM) inhibited high-threshold Ca2+ channel current by an average of 42% in type 1 DRG cells, compared with 15%, 18%, and 7% inhibition in types 2-4, respectively. Similarly, (+)8-OH-DPAT (1 microM) inhibited high-threshold Ca2+ channel current by an average of 35% in type 1 DRG cells, compared with 5%, 8%, and 3% inhibition in types 2-4, respectively. 7. It is possible that DRG cells that vary in their expression of membrane properties may represent sensory neurons that transmit different types of sensory information. Thus the variation in inhibition of Ca2+ channel current by 5-HT and (+)8-OH-DPAT in the above categories of DRG cells may indicate that 5-HT1A receptor activation inhibits Ca2+ entry into some types of DRG sensory neurons more than others.

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