Inositol 1,4,5-Triphosphate-Evoked Responses in Midbrain Dopamine Neurons

• Published in: The Journal of neuroscience 2000-10, Vol.20 (20), p.103-RC103
• Main Authors: Morikawa, Hitoshi, Imani, Farzin, Khodakhah, Kamran, Williams, John T
• Format: Article
• Language: English
• Subjects: Animals; Apamin - pharmacology; Calcium - metabolism; Calcium-Transporting ATPases - antagonists & inhibitors; Dopamine - metabolism; Dose-Response Relationship, Drug; In Vitro Techniques; Inositol 1,4,5-Trisphosphate - analogs & derivatives; Inositol 1,4,5-Trisphosphate - metabolism; Inositol 1,4,5-Trisphosphate - pharmacology; Intracellular Fluid - metabolism; Mesencephalon - cytology; Mesencephalon - drug effects; Mesencephalon - metabolism; Neurons - drug effects; Neurons - metabolism; Patch-Clamp Techniques; Photolysis; Potassium Channels - drug effects; Potassium Channels - metabolism; Potassium Channels, Calcium-Activated; Rapid Communication; Rats; Rats, Wistar; Ryanodine Receptor Calcium Release Channel - genetics; Ryanodine Receptor Calcium Release Channel - metabolism; Signal Transduction - drug effects; Small-Conductance Calcium-Activated Potassium Channels
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.20-20-j0003.2000

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.