LOCAL-ANESTHETICS DEPRESS THE CALCIUM CURRENT OF RAT SENSORY NEURONS IN CULTURE

Background: Local anesthetics are known to inhibit the voltage-gated s odium current (I-Na) of the nerve membrane, but it has not been fully studied whether anesthetic concentrations of local anesthetics depress the voltage-gated calcium current (I-Ca) of mammalian neurons. The ef fects of local anesthetics on I-Ca evoked in cultured rat dorsal root ganglion cells were studied. Methods: Whole cell patch clamp recording s were made from rat dorsal root ganglion cells cultured for 1-3 weeks . I,was recorded using patch electrodes filled with Cs-aspartate in Na +- free external solution containing 5 mM-Ba2+. All drugs, including l ocal anesthetics, were applied by miniperfusion from micropipettes by pressure ejection. Results: Tetracaine (300 mu M) depressed the peak a mplitudes of high voltage-activated (HVA)-I-Ca to 22.6 +/- 8.8% of con trol values (n = 14) without affecting the current-voltage relation. A tetracaine dose-response curve for HVA-I-CA indicated an apparent dis sociation constant of 73.5 mu M. Tetracaine (30 mu M) depressed nicard ipine-sensitive HVA-I-Ca (L-type) to 14.3 +/- 6.7% (n = 6), omega-cono toxin-sensitive HVA-I-Ca (N-type) to 81.6 +/- 9.6% (n = 7), and low vo ltage-activated (LVA)-I-Ca (T-type) to 65.1 +/- 11.1% (n = 6) of their respective controls. Local anesthetics other than tetracaine also dep ressed HVA-I-Ca but were of different potency; the rank sequence was d ibucaine > tetracaine > bupivacaine much greater than procaine = lidoc aine. Conclusions: These results suggest that both HVA-I-Ca and LVA-I- Ca are depressed by tetracaine used at the concentrations required for spinal anesthesia and that the L-type Ca2+ channel among Ca2+ channel subtypes is the most susceptible to tetracaine. A good correlation be tween local anesthetic potencies to inhibit HVA-I-Ca and their anesthe tic potencies implies that the inhibition of calcium influx through vo ltage-gated channels may contribute to spinal anesthetic mechanisms.