PMID- 24225021 OWN - NLM STAT- MEDLINE DCOM- 20140407 LR - 20211203 IS - 1471-2202 (Electronic) IS - 1471-2202 (Linking) VI - 14 DP - 2013 Nov 13 TI - Dopaminergic tone regulates transient potassium current maximal conductance through a translational mechanism requiring D1Rs, cAMP/PKA, Erk and mTOR. PG - 143 LID - 10.1186/1471-2202-14-143 [doi] AB - BACKGROUND: Dopamine (DA) can produce divergent effects at different time scales. DA has opposing immediate and long-term effects on the transient potassium current (IA) within neurons of the pyloric network, in the Panulirus interruptus stomatogastric ganglion. The lateral pyloric neuron (LP) expresses type 1 DA receptors (D1Rs). A 10 min application of 5-100 muM DA decreases LP IA by producing a decrease in IA maximal conductance (Gmax) and a depolarizing shift in IA voltage dependence through a cAMP-Protein kinase A (PKA) dependent mechanism. Alternatively, a 1 hr application of DA (>/=5 nM) generates a persistent (measured 4 hr after DA washout) increase in IA Gmax in the same neuron, through a mechanistic target of rapamycin (mTOR) dependent translational mechanism. We examined the dose, time and protein dependencies of the persistent DA effect. RESULTS: We found that disrupting normal modulatory tone decreased LP IA. Addition of 500 pM-5 nM DA to the saline for 1 hr prevented this decrease, and in the case of a 5 nM DA application, the effect was sustained for >4 hrs after DA removal. To determine if increased cAMP mediated the persistent effect of 5nM DA, we applied the cAMP analog, 8-bromo-cAMP alone or with rapamycin for 1 hr, followed by wash and TEVC. 8-bromo-cAMP induced an increase in IA Gmax, which was blocked by rapamycin. Next we tested the roles of PKA and guanine exchange factor protein activated by cAMP (ePACs) in the DA-induced persistent change in IA using the PKA specific antagonist Rp-cAMP and the ePAC specific agonist 8-pCPT-2'-O-Me-cAMP. The PKA antagonist blocked the DA induced increases in LP IA Gmax, whereas the ePAC agonist did not induce an increase in LP IA Gmax. Finally we tested whether extracellular signal regulated kinase (Erk) activity was necessary for the persistent effect by co-application of Erk antagonists PD98059 or U0126 with DA. Erk antagonism blocked the DA induced persistent increase in LP IA. CONCLUSIONS: These data suggest that dopaminergic tone regulates ion channel density in a concentration and time dependent manner. The D1R- PKA axis, along with Erk and mTOR are necessary for the persistent increase in LP IA induced by high affinity D1Rs. FAU - Rodgers, Edmund W AU - Rodgers EW FAU - Krenz, Wulf-Dieter AU - Krenz WD FAU - Jiang, Xiaoyue AU - Jiang X FAU - Li, Lingjun AU - Li L FAU - Baro, Deborah J AU - Baro DJ AD - Department of Biology, Georgia State University, Atlanta 30303, Georgia. dbaro@gsu.edu. LA - eng GR - R01 DA024039/DA/NIDA NIH HHS/United States GR - DA024039/DA/NIDA NIH HHS/United States GR - R01 DK071801/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20131113 PL - England TA - BMC Neurosci JT - BMC neuroscience JID - 100966986 RN - 0 (Potassium Channels) RN - 0 (Receptors, Dopamine) RN - E0399OZS9N (Cyclic AMP) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - Cyclic AMP/metabolism MH - Cyclic AMP-Dependent Protein Kinases/metabolism MH - Dopamine/*metabolism MH - Extracellular Signal-Regulated MAP Kinases/physiology MH - Ganglia, Invertebrate/physiology MH - Membrane Potentials/*physiology MH - Neurons/*metabolism MH - Palinuridae MH - Patch-Clamp Techniques MH - Potassium Channels/*metabolism MH - Pylorus/innervation/metabolism MH - Receptors, Dopamine/metabolism MH - Signal Transduction/*physiology MH - TOR Serine-Threonine Kinases/metabolism PMC - PMC3840709 EDAT- 2013/11/15 06:00 MHDA- 2014/04/08 06:00 PMCR- 2013/11/13 CRDT- 2013/11/15 06:00 PHST- 2013/06/21 00:00 [received] PHST- 2013/11/07 00:00 [accepted] PHST- 2013/11/15 06:00 [entrez] PHST- 2013/11/15 06:00 [pubmed] PHST- 2014/04/08 06:00 [medline] PHST- 2013/11/13 00:00 [pmc-release] AID - 1471-2202-14-143 [pii] AID - 10.1186/1471-2202-14-143 [doi] PST - epublish SO - BMC Neurosci. 2013 Nov 13;14:143. doi: 10.1186/1471-2202-14-143.