VARIATION IN SEROTONERGIC INHIBITION OF CALCIUM-CHANNEL CURRENTS IN 4TYPES OF RAT SENSORY NEURONS DIFFERENTIATED BY MEMBRANE-PROPERTIES

1. Rat dorsal root ganglion (DRG) cell bodies were screened according to action potential (AP) duration, capsaicin sensitivity, expression o f I-H, I-A, 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 c urrent at a holding potential (HP) of -60 mV by 1 mu M capsaicin. I-H was evoked by a 787-ms hyperpolarization to -110 mV from an HP of -60 mV. I-A was evoked by repolarization to -60 mV after a 787-ms hyperpol arization to -110 mV. High-threshold Ca2+ channel current was evoked b y a depolarization to -10 or 0 mV from an HP of -60 mV, and L- and N-t ype Ca2+ channel current was fractionated using selective Ca2+ channel blockers (nimodipine and omega-conotoxin GVIA). T-type Ca2+ channel c urrent 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 fo ur categories, referred to as types 1-4, are described below. 2. Type 1 DRG cells (soma diameter 24.6 +/- 0.5 mu m, 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 I-H or I-A 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 Ca2channel currents averaged 245 pA. 3. Type 2 DRG cells (soma diameter 2 5.2 +/- 0.9 mu m, n = 19) had short-duration APs (average = 2.9 ms) wi th a small shoulder on the falling limb and were capsaicin sensitive. I-H was negligible but I-A averaged 184 pA. High-threshold Ca2+ channe l current averaged 42% N-type, 23% L-type, and 35% resistant. T-type C a2+ channel currents averaged 47 pA. 4. Type 3 DRG cells (soma diamete r 18.6 +/- 0.8 mu m, n = 21) had short-duration APs (average = 1.8 ms) and were insensitive to capsaicin. I-A was not expressed but I-H aver aged 147 pA. High-threshold Ca2+ channel current averaged 27% N-type, 44% L-type, and 29% resistant. T-type Ca2+ channel currents averaged 3 06 pA. 5. Type 4 DRG cells (soma diameter 33.9 +/- 0.4 mu m, n = 23) h ad short-duration APs (average = 1.1 ms) and were capsaicin insensitiv e. I-A was not expressed but I-H averaged 810 pA. High-threshold Ca2channel current was 16% N-type, 4% L-type, and 80% resistant. T-type C a2+ 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 aver age, 5-HT (10 mu M) inhibited high-threshold Ca2+ channel current by a n average of 42% in type 1 DRG cells, compared with 15%, 18%, and 7% i nhibition in types 2-4, respectively. Similarly, (+)8-OH-DPAT (1 mu M) 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 e xpression of membrane properties may represent sensory neurons that tr ansmit different types of sensory information. Thus the variation in i nhibition of Ca2+ channel current by 5-HT and (+)8-OH-DPAT in the abov e categories of DRG cells may indicate that 5-HT1A receptor activation inhibits Ca2+ entry into some types of DRG sensory neurons more than others.