Inositol 1,4,5-triphosphate-evoked responses in midbrain dopamine neurons.

H. Morikawa, F. Imani, K. Khodakhah, J. T. Williams

Research output: Contribution to journalArticle

67 Scopus citations


Synaptically released glutamate evokes slow IPSPs mediated by metabotropic glutamate receptors (mGluRs) in midbrain dopamine neurons. These mGluR IPSPs are caused by release of Ca(2+) from intracellular stores and subsequent activation of small-conductance Ca(2+)-activated K(+) channels (SK channels). To further investigate the intracellular mechanisms involved, the effect of photolyzing intracellular caged inositol 1,4,5-triphosphate (InsP(3)) on membrane conductance and intracellular Ca(2+) concentration ([Ca(2+)](i)) was examined in rat midbrain slices. Photolytic release of InsP(3) elicited a transient outward current and a sharp rise in [Ca(2+)](i) that lasted for approximately 5 sec. Apamin, a blocker of SK channels, abolished the InsP(3)-induced outward current without affecting the rise in [Ca(2+)](i). Depleting intracellular Ca(2+) stores with cyclopiazonic acid completely blocked both the outward current and the Ca(2+) transient elicited by InsP(3). InsP(3)-evoked Ca(2+) mobilization was not affected by blockade of ryanodine receptors with ruthenium red, whereas depleting ryanodine-sensitive Ca(2+) stores with ryanodine almost eliminated InsP(3)-induced Ca(2+) release. Increasing the size of intracellular Ca(2+) stores by means of prolonged depolarization added a late component to the outward current and a slow component to the rising phase of [Ca(2+)](i). These effects of depolarization were blocked by ruthenium red. These results show that InsP(3) activates SK channels by releasing Ca(2+) from InsP(3)-sensitive stores that also contain ryanodine receptors. Increasing intracellular Ca(2+) stores boosts InsP(3)-evoked responses by invoking Ca(2+)-induced Ca(2+) release through ryanodine receptors. This intracellular signaling pathway may play a significant role in regulating the excitability of midbrain dopamine neurons.

Original languageEnglish (US)
Pages (from-to)RC103
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Issue number20
StatePublished - Oct 15 2000

ASJC Scopus subject areas

  • Neuroscience(all)

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