Ionic dependencies of tetrodotoxin-resistant action potentials in trigeminal root ganglion neurons.

Action potentials recorded in vitro from the perikarya of trigeminal root ganglion neurons (guinea-pig) were examined for their sensitivities to blockers of specific ion channels or to removal of certain ionic species in the bathing media. The majority (approximately 65%) of the 137 neurons exhibited action potentials following application of the Na(+)-channel blocker, tetrodotoxin. This group of neurons was selected for further investigation under conditions of extracellular K(+)-channel blockade with tetraethylammonium and 4-aminopyridine. Long-duration action potentials consisting of two distinct components could be evoked under such conditions. The fast component of the spike was abolished in Na(+)-deficient perfusion media and was sensitive to blockade by extracellular lidocaine or intracellular QX-222 applications. It is likely that the slow component was mediated mainly by Ca2+, but in Ca2(+)-deficient media. Mg2(+)-influx may have contributed to the small voltage response. The amplitude and shape of the slow component was unaffected by applications of lidocaine or QX-222. Self-sustained repetitive firing was also observed in 11 neurons in the above conditions. This activity persisted even under conditions of severe deficiencies in extracellular [Ca2+] or [Na+]. Two distinct but overlapping K(+)-conductances that were sensitive to blockade by internal Cs(+)-application and insensitive to applications of tetraethylammonium and 4-aminopyridine, appear to mediate the afterhyperpolarization of the long-duration spike. One portion of the afterhyperpolarization was 60-150 ms in duration and was unaffected by removal of Ca2+ from the extracellular media, while the other had a time-course lasting 150-250 ms and was abolished by removal of external Ca2+. In some neurons, these K(+)-conductances were blocked by high doses of doxorubicin or cisplatin. The results show that at least two ion species (Na+ and Ca2+) contribute to the formation of the tetrodotoxin-resistant, long-duration action potential in trigeminal root ganglion neurons during selective K(+)-conductance blockade and also provide evidence for Mg2+ involvement in the generation of this voltage response.