Cell specific dopamine modulation of the transient potassium current in the pyloric network by the canonical D1 receptor signal transduction cascade.
Dopamine (DA) modifies the motor pattern generated by the pyloric network in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus, by directly acting on each of the circuit neurons. The 14 pyloric neurons fall into six cell types, and DA actions are cell type specific. The transient potassium current mediated by shal channels (I(A)) is a common target of DA modulation in most cell types. DA shifts the voltage dependence of I(A) in opposing directions in pyloric dilator (PD) versus lateral pyloric (LP) neurons. The mechanism(s) underpinning cell-type specific DA modulation of I(A) is unknown. DA receptors (DARs) can be classified as type 1 (D1R) or type 2 (D2R). D1Rs and D2Rs are known to increase and decrease intracellular cAMP concentrations, respectively. We hypothesized that the opposing DA effects on PD and LP I(A) were due to differences in DAR expression patterns. In the present study, we found that LP expressed somatodendritic D1Rs that were concentrated near synapses but did not express D2Rs. Consistently, DA modulation of LP I(A) was mediated by a Gs-adenylyl cyclase-cAMP-protein kinase A pathway. Additionally, we defined antagonists for lobster D1Rs (flupenthixol) and D2Rs (metoclopramide) in a heterologous expression system and showed that DA modulation of LP I(A) was blocked by flupenthixol but not by metoclopramide. We previously showed that PD neurons express D2Rs, but not D1Rs, thus supporting the idea that cell specific effects of DA on I(A) are due to differences in receptor expression.
Department of Biology, Georgia State University, Atlanta, Georgia 30302-4010, USA.
Hongmei
H
Zhang
Edmund W
EW
Rodgers
Wulf-Dieter C
WD
Krenz
Merry C
MC
Clark
Deborah J
DJ
Baro
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D017952:Ganglia, Invertebrate / Q000166:cytology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects*; D033521:Palinuridae; D018408:Patch-Clamp Techniques / Q000379:methods; D010742:Phospholipid Ethers / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011708:Pylorus / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D018492:Dopamine Antagonists; D007546:Isoquinolines; D010742:Phospholipid Ethers; D026902:Potassium Channel Blockers; D047428:Protein Kinase Inhibitors; D017447:Receptors, Dopamine D1; D013449:Sulfonamides; D005576:Colforsin; C026659:edelfosine; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D000242:Cyclic AMP; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D011188:Potassium; D004298:Dopamine