ATP modulation of sodium currents in rat dorsal root ganglion neurons.
The modulation of tetrodotoxin-sensitive (TTX-S) and slow tetrodotoxin-resistant (TTX-R) sodium currents in rat dorsal root ganglion neurons by ATP was studied using the whole-cell patch-clamp method. The effects of ATP on two types of sodium currents were either stimulatory or inhibitory depending on the kinetic parameters tested. At a holding potential of -80 mV ATP suppressed TTX-S sodium currents when the depolarizing potential was positive to -30 mV but it increased them when the depolarizing potential was negative to -30 mV. At the same holding potential slow TTX-R sodium currents were always increased by ATP regardless of the depolarizing potential. In both types of sodium currents ATP shifted both the conductance-voltage relationship curve and the steady-state inactivation curve in the hyperpolarizing direction, and accelerated the time-dependent inactivation. ATP decreased the maximum conductance of TTX-S sodium currents but increased that of slow TTX-R sodium currents. The results suggest that ATP would decrease the excitability of neurons with TTX-S sodium channels but would increase that of neurons with slow TTX-R sodium channels. The effects of ATP on sodium currents were preserved in the presence of a G-protein inhibitor, GDP-beta-S, or purinergic antagonists, suramin and Reactive Blue-2, suggesting that purinergic receptors might not be involved in ATP modulation of sodium currents.
Joo Choi
Eun
E
Department of Pharmacology, Chung-Ang University, College of Medicine, 221 Heuk-Suk Dong, Dong-Jak Ku, 156-756, Seoul, South Korea. jinhos@cau.ac.kr
Hong
Min Pyo
MP
Kyoo Shin
Yong
Y
Soo Lee
Chung
C
Park
Mijung
M
Song
Jin Ho
JH
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000970:Antineoplastic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D058914:Purinergic Antagonists; D051381:Rats; D015222:Sodium Channels / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D014227:Triazines / Q000494:pharmacology
D000779:Anesthetics, Local; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D058914:Purinergic Antagonists; D015222:Sodium Channels; D013873:Thionucleotides; D014227:Triazines; D006153:Guanosine Diphosphate; D013779:Tetrodotoxin; C012842:Cibacron Blue F 3GA; D013498:Suramin; C023427:guanosine 5'-O-(2-thiodiphosphate); D000255:Adenosine Triphosphate