Inhibitory action of muscarinic agonists on neurons in the rat laterodorsal tegmental nucleus in vitro.
1. The effects of the mixed cholinergic agonist carbachol and the muscarinic agonist methacholine (MCh) on neurons of the laterodorsal tegmental nucleus (LDT) were studied with the use of intracellular and whole-cell patch-clamp recordings in a rat brain stem slice preparation. 2. Neurons were classified into one of two categories on the basis of their intrinsic membrane properties: those that displayed a prominent low-threshold calcium burst (LTB, 60%) and those that did not exhibit such a burst (non-LTB, 40%). 3. Neurons from which recordings were obtained were filled with biocytin, visualized with Texas-red avidin, and identified as cholinergic or noncholinergic with NADPH-diaphorase histochemistry. Eighty percent of the LTB neurons that were processed in this manner were cholinergic, and 60% of the non-LTB neurons were cholinergic. 4. Carbachol elicited a membrane hyperpolarization associated with a decrease in input resistance in 95% of the cells tested. Under voltage clamp this response was shown to be due to an outward current that reversed near the equilibrium potential for potassium and displayed marked inward rectification. The conductance/voltage relationship was fit to the Boltzmann equation with a mean V1/2 = -73 +/- 4 (SD) mV and a mean k value of 10 +/- 4. The carbachol-evoked current was fully blocked by extracellular barium. 5. There was no significant effect of carbachol on the transient currents IA or IT. 6. The carbachol-evoked current was mimicked by the specific muscarinic agonist methacholine and blocked by high concentrations of the muscarinic receptor antagonist pirenzepine (IC50 = 580 nM).(ABSTRACT TRUNCATED AT 250 WORDS)
Luebke
J I
JI
Department of Psychiatry, Harvard Medical School, Brockton, Massachusetts 02401.
McCarley
R W
RW
Greene
R W
RW
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001931:Brain Mapping; D002217:Carbachol / Q000494:pharmacology*; D046508:Culture Techniques; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013681:Tegmentum Mesencephali / Q000187:drug effects* / Q000502:physiology
D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; D002217:Carbachol; D000109:Acetylcholine