Prostaglandin E sub(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 sub(Ca)) in acutely isolated mouse trigeminal sensory neurons, using standard whole cell voltage clamp techniques. Trigeminal neurons were divided int...
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Veröffentlicht in: | The Journal of physiology 2002-03, Vol.539 (2), p.433-444 |
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Sprache: | eng |
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Zusammenfassung: | Prostaglandins are important mediators of pain and inflammation. We have examined the effects of prostanoids on voltage-activated calcium currents (I sub(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 sub(Ca). The absence of T-type I sub(Ca) is highly correlated with sensitivity to mu -opioid agonists and the VR1 agonist capsaicin. In both populations of cells, high voltage-activated I sub(Ca) was inhibited by PGE sub(2) with an EC sub(50) of about 35 nM, to a maximum of 30 %. T-type I sub(Ca) was not inhibited by PGE sub(2). Pertussis toxin pre-treatment abolished the effects of PGE sub(2) in Type 2 cells, but not in Type 1 cells, whereas treatment with cholera toxin prevented the effects of PGE sub(2) in Type 1 cells, but not in Type 2 cells. Inhibition of I sub(Ca) by PGE sub(2) was associated with slowing of current activation and could be relieved with a large positive pre-pulse, consistent with inhibition of I sub(Ca) by G protein beta gamma 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 sub(2) were only mimicked by the selective EP sub(3) receptor agonist ONO-AE-248, and not by selective agonists for EP sub(1) (ONO-DI-004), EP sub(2) (ONO-AE1-259) and EP sub(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 sub(2)-mediated inhibition of calcium channels, with Gi/Go type G proteins involved in one population, and Gs type G proteins in the other. |
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ISSN: | 0022-3751 |
DOI: | 10.1113/jphysiol.2001.013322 |