Regulation of dopamine-induced Na+ current response by small G-protein RhoB or C and phospholipase D in Aplysia neurons.
A family of GTP-binding proteins, Rho, plays critical roles in cell migration, morphological change, cytokinesis, and smooth muscle contraction. Furthermore, evidence has recently been accumulating for an involvement in regulation of receptor-operated ionic channels. We previously reported that stimulation of D1-like receptor by dopamine (DA) induces a slow Na+ current response in the identified neurons of Aplysia under voltage-clamp. To further study a regulatory mechanism of the DA-induced response, we examined possible involvement of small G-proteins and subsequent enzymes. The Na+ current response to DA was gradually and irreversibly depressed after the intracellular injection of either Clostridium difficile toxin B, an inhibitor for all Rho family G-proteins, or Clostridium botulinum C3 exoenzyme, a specific blocker for RhoA-C. Intacellular injection of active RhoA had no significant effect on the response. However, injection of GAP domain of p50RhoGAP significantly depressed the DA-induced response, while application of GEF domain of RhoGEF Dbs increased the response. In addition, either intracellular injection of alpha-synuclein or extracellular application of 1-butanol, inhibitors for phospholipase D (PLD), significantly depressed the DA-induced response. These results suggest that the DA-induced Na+ current response may be facilitated by the activation of Rho family G-protein RhoB or C but not RhoA, and subsequent PLD.
Kawasaki
Satoshi
S
Department of Physiology and Advanced Medical Science Research Center, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan. skawasak@iwate-med.ac.jp
Watanabe
Shuji
S
Kimura
Shingo
S
Fujita
Reiko
R
Ochiai
Jin
J
Sasaki
Kazuhiko
K
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D001048:Aplysia; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017952:Ganglia, Invertebrate / Q000166:cytology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D010739:Phospholipase D / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D004791:Enzyme Inhibitors; D015222:Sodium Channels; D010739:Phospholipase D; D020741:rho GTP-Binding Proteins; D000109:Acetylcholine; D004298:Dopamine