Cellular mechanisms of nociception in the frog.
Cellular mechanisms underlying defense reactions induced by noxious heat and acids were studied in frogs (Rana pipiens) by measuring whole cell membrane currents in cultured dorsal root ganglion (DRG) neurons. Seventy-eight of 82 DRG neurons exposed to 3-s ramps of increasing temperature to 48 degrees C exhibited an inward current (I(HEAT)) of 490 +/- 70 pA at -70 mV. I(HEAT) exhibited reversal at approximately 10 mV with a pronounced outward rectification, suggesting opening of nonselective cation channels. In frogs, in contrast to mammals, I(HEAT) was not influenced by capsaicin (5 microM), capsazepine (10 microM), or ruthenium red (10 microM). In a large proportion (approximately 80%) of heat-sensitive DRG neurons, acids produced a large slowly inactivating sodium carried current (I(ACID)) with average pH(50) 5.7. I(ACID) was blocked by 1 mM amiloride (to 22%) and was absent if extracellular Na(+) was substituted by Cs(+). Elevating temperature to 38 degrees C increased I(ACID), whereas temperatures >40 degrees C profoundly inhibited it (by 82 +/- 2%; n = 42). The inhibition was long-lasting (>30 s) but fully reversible. Phorbol ester myristate acetate (PMA, 1 microM) and forskolin (1 microM) inhibited I(ACID) to 37 +/- 5% (n = 5) and 78 +/- 8% (n = 4), respectively. It is suggested that I(HEAT) in frog DRG neurons is carried through capsaicin-insensitive nonselective cation channels distinct from vanilloid receptor in mammals, whereas I(ACID) is carried through amiloride-sensitive sodium channels that are strongly inhibited by noxious heat, possibly due to activation of the intracellular messenger systems.
D000143:Acids; D000367:Age Factors; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology* / Q000502:physiology; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D011894:Rana pipiens; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000143:Acids; D002273:Carcinogens; D005576:Colforsin; D013755:Tetradecanoylphorbol Acetate; D002211:Capsaicin