Prostaglandin E(2) inhibits calcium current in two sub-populations of acutely isolated mouse trigeminal sensory neurons.
Prostaglandins are important mediators of pain and inflammation. We have examined the effects of prostanoids on voltage-activated calcium currents (I(Ca)) in acutely isolated mouse trigeminal sensory neurons, using standard whole cell voltage clamp techniques. Trigeminal neurons were divided into two populations based on the presence (Type 2) or absence (Type 1) of low voltage-activated T-type I(Ca). The absence of T-type I(Ca) is highly correlated with sensitivity to mu-opioid agonists and the VR1 agonist capsaicin. In both populations of cells, high voltage-activated I(Ca) was inhibited by PGE(2) with an EC(50) of about 35 nM, to a maximum of 30 %. T-type I(Ca) was not inhibited by PGE(2). Pertussis toxin pre-treatment abolished the effects of PGE(2) in Type 2 cells, but not in Type 1 cells, whereas treatment with cholera toxin prevented the effects of PGE(2) in Type 1 cells, but not in Type 2 cells. Inhibition of I(Ca) by PGE(2) was associated with slowing of current activation and could be relieved with a large positive pre-pulse, consistent with inhibition of I(Ca) by G protein betagamma subunits. Reverse transcription-polymerase chain reaction of mRNA from trigeminal ganglia indicated that all four EP prostanoid receptors were present. However, in both Type 1 and Type 2 cells the effects of PGE(2) were only mimicked by the selective EP(3) receptor agonist ONO-AE-248, and not by selective agonists for EP(1) (ONO-DI-004), EP(2) (ONO-AE1-259) and EP(4) (ONO-AE1-329) receptors. These data indicate that two populations of neurons in trigeminal ganglia differing in their calcium channel expression, sensitivity to mu-opioids and capsaicin also have divergent mechanisms of PGE(2)-mediated inhibition of calcium channels, with Gi/Go type G proteins involved in one population, and Gs type G proteins in the other.
Borgland
Stephanie L
SL
Department of Pharmacology, University of Sydney, NSW, 2006, Australia.
Connor
Mark
M
Ryan
Renae M
RM
Ball
Helen J
HJ
Christie
MacDonald J
MJ
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism; D020907:Calcium Channels, Q-Type / Q000187:drug effects / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000187:drug effects / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009475:Neurons, Afferent / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014276:Trigeminal Nerve / Q000187:drug effects / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D020907:Calcium Channels, Q-Type; D010566:Virulence Factors, Bordetella; D012313:RNA; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs; D015232:Dinoprostone