Regulation of dopamine-induced Na+ current response by small G-protein RhoB or C and phospholipase D in Aplysia neurons |
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Authors: | Kawasaki Satoshi Watanabe Shuji Kimura Shingo Fujita Reiko Ochiai Jin Sasaki Kazuhiko |
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Institution: | Department of Physiology and Advanced Medical Science Research Center, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan. skawasak@iwate-med.ac.jp |
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Abstract: | 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. |
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