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This Article Full Text Full Text (PDF) All Versions of this Article: 90/4/2115    most recent 00442.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Komagiri, Y. Articles by Kitamura, N. Search for Related Content PubMed PubMed Citation Articles by Komagiri, Y. Articles by Kitamura, N.

Effect of Intracellular Dialysis of ATP on the Hyperpolarization-Activated Cation Current in Rat Dorsal Root Ganglion Neurons

Laboratory of Physiology, Department of Biomedical Sciences, the Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan

Submitted 8 May 2003; accepted in final form 1 July 2003

The mechanism of the effect of intracellular ATP on the hyperpolarization-activated non-selective cation current (I_h) in rat dorsal root ganglion neurons was investigated using a whole cell voltage-clamp technique. Under voltage-clamp conditions, I_h was activated by hyperpolarizing pulses raised to a voltage of between –70 and –130 mV. The activation curve of I_h in rat dorsal root ganglion (DRG) neurons shifted by about 15 mV in the positive direction with an intracellular solution containing 1 mM cAMP. When ATP (2 mM) was applied intracellularly, the half-maximal activation voltage (V_half) of I_h shifted from –97.4 ± 1.9 to –86.8 ± 1.6 mV, resulting in an increase in the current amplitude of I_h by the pulse to between –80 and –90 mV. In the presence of an adenylate cyclase inhibitor, SQ-22536 (100 µM), the intracellular dialysis of ATP also produced a shift in the voltage-dependence of I_h in rat DRG neurons, indicating that the effect of ATP was not caused by cAMP converted by adenylate cyclase. Intracellular dialysis of a nonhydrolysable ATP analog, AMP-PNP or ATP--S, also produced a positive shift in the voltage-dependence of I_h activation, suggesting that the effect of ATP results from its direct action on the channel protein. These results indicate that cytosolic ATP directly regulates the voltage dependence of I_h activation as an intracellular modulating factor.