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KMID : 0613820190290091010
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Journal of Life Science
2019 Volume.29 No. 9 p.1010 ~ p.1015
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Effects of Olanzapine on the Pacemaker Potentials of Interstitial Cells of Cajal in Murine Small Intestine
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Kim Byung-Joo
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Abstract
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The interstitial cells of Cajal (ICCs) are the pacemaker cells in the gastrointestinal (GI) tract. In the present study, the effects of olanzapine, an atypical antipsychotic agent, on pacemaker potentials in cultured ICCs from the small intestine of the mouse were investigated. The whole-cell patch-clamp configuration was used to record pacemaker potentials from cultured ICCs. Olanzapine produced pacemaker depolarizations in a concentration-dependent manner in current clamp mode. Methoctramine, a muscarinic M2 receptor antagonist, did not inhibit olanzapine-induced pacemaker depolarizations, whereas 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) muscarinic M3 receptor antagonist did inhibit it. When guanosine 5'-[β-thio] diphosphate (GDP-β-S; 1 mM) was in the pipette solution, olanzapine-induced pacemaker depolarization was blocked. Also, low Na+ solution externally eliminated the generation of pacemaker potentials and inhibited the olanzapine-induced pacemaker depolarizations. Additionally, the nonselective cation channel blocker, flufenamic acid, inhibited the olanzapine-induced pacemaker depolarizations. Pretreatment with U-73122, an active phospholipase C (PLC) inhibitor, also eliminated the generation of pacemaker potentials and suppressed the olanzapine-induced pacemaker depolarizations. These results suggested that olanzapine modulates the pacemaker potentials through muscarinic M3 receptor activation by G protein?dependent external Na+ and PLC pathway in the ICCs. Therefore, olanzapine could affect intestinal motility through ICCs.
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KEYWORD
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Gastrointestinal tract, ICCs, interstitial cells of Cajal, olanzapine, pacemaker potentials
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