Prostaglandin E2 inhibits calcium current in two sub-populations of acutely isolated mouse trigeminal sensory neurons

Stephanie L. Borgland, Mark Connor*, Renae M. Ryan, Helen J. Ball, Mac Donald J Christie

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

Prostaglandins are important mediators of pain and inflammation. We have examined the effects of prostanoids on voltage-activated calcium currents (ICa) 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 ICa. The absence of T-type ICa is highly correlated with sensitivity to μ-opioid agonists and the VR1 agonist capsaicin. In both populations of cells, high voltage-activated ICa was inhibited by PGE2 with an EC50 of about 35 nM, to a maximum of 30%. T-type ICa was not inhibited by PGE2. Pertussis toxin pre-treatment abolished the effects of PGE2 in Type 2 cells, but not in Type 1 cells, whereas treatment with cholera toxin prevented the effects of PGE2 in Type 1 cells, but not in Type 2 cells. Inhibition of ICa by PGE2 was associated with slowing of current activation and could be relieved with a large positive pre-pulse, consistent with inhibition of ICa by G protein βγ 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 PGE2 were only mimicked by the selective EP3 receptor agonist ONO-AE-248, and not by selective agonists for EP1 (ONO-DI-004), EP2 (ONO-AE1-259) and EP4 (ONO-AE1-329) receptors. These data indicate that two populations of neurons in trigeminal ganglia differing in their calcium channel expression, sensitivity to μ-opioids and capsaicin also have divergent mechanisms of PGE2-mediated inhibition of calcium channels, with Gi/Go type G proteins involved in one population, and Gs type G proteins in the other.

Original languageEnglish
Pages (from-to)433-444
Number of pages12
JournalJournal of Physiology
Volume539
Issue number2
DOIs
Publication statusPublished - 1 Mar 2002
Externally publishedYes

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