Modulation of voltage-activated Ca currents by pain-inducing agents in a dorsal root ganglion neuronal line, F-11.
Whole cell currents evoked by pain-inducing agents--bradykinin (Bk), capsaicin (Cap), and reciniferatoxin (RTX), and their modulation of voltage-activated Ca currents were examined in F-11 cells using a patch electrode voltage clamp technique. Most F-11 cells generated action potentials under current clamp if their membrane potentials were held sufficiently negative. Average peak inward Na current (INa) was 100 microA/cm2 and the INa was abolished by 10(-6) M tetrodotoxin. At least two types of Ca currents could be clearly distinguished on the basis of voltage dependency and kinetics; a low threshold transient ICa(t) and a high threshold sustained ICa(l). In addition, another high threshold transient Ca current, presumably ICa(n), was observed. About 30% of the cells produced inward current for these pain-inducing agents, when activated at the membrane holding potential of -70 mV. In some F-11 cells, the amplitude of action potential was observed to increase during 10(-6) M Cap-induced depolarization. Both low and high threshold Ca currents were reduced by 10(-6) M Bk in the majority of the cells. Similarly, both 10(-6) M Cap and 10(-9) M RTX reduced these Ca currents. However, a considerable number of cells showed an initial enhancement followed by reduction in the amplitude of these Ca currents. With higher concentrations of these ligands, all Ca currents were suppressed. Such modulation of voltage-activated Ca currents by pain-inducing agents occurred in both the presence and absence of apparent receptor-activated current flows in the cells. In pertussis toxin (PTX)-treated cells, the inhibitory modulation of Ca currents by pain-inducing agents was suppressed. In contrast, in cholera toxin (CTX)-treated cells, this inhibitory modulation appeared to be enhanced. These data indicate that the inhibitory modulation of Ca channel currents by Cap and RTX, similarly to that of Bk, involves a PTX-sensitive inhibitory G protein (Gi).
Kusano
K
K
Laboratory of Neurochemistry, National Institute of Neurological Disease and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Gainer
H
H
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D002460:Cell Line; D004224:Diterpenes / Q000494:pharmacology; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000502:physiology*; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000096:biosynthesis / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004224:Diterpenes; D010456:Peptides, Cyclic; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D020960:omega-Conotoxins; C053423:Conus magus toxin; D013779:Tetrodotoxin; C024353:resiniferatoxin; D002211:Capsaicin; D001920:Bradykinin