PMID- 2657440 OWN - NLM STAT- MEDLINE DCOM- 19890707 LR - 20190725 IS - 0028-1298 (Print) IS - 0028-1298 (Linking) VI - 339 IP - 1-2 DP - 1989 Jan-Feb TI - Anti-cholinergic effect of verapamil on the muscarinic acetylcholine receptor-gated K+ channel in isolated guinea-pig atrial myocytes. PG - 244-6 AB - Effects of verapamil on the acetylcholine (ACh)-induced K+ current were examined in single atrial cells, using the tight-seal whole-cell clamp technique. The pipette solution contained guanosine-5'-triphosphate (GTP) or guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma S, a non-hydrolysable GTP analogue). In GTP-loaded cells, ACh induced a specific K+ current, which is known to be mediated by pertussis toxin-sensitive GTP-binding (G) proteins. Verapamil (0.1-100 microM) depressed the ACh-induced K+ current in a concentration-dependent fashion. In GTP-gamma S-loaded cells, the K+ current remained persistently after wash-out of ACh, probably due to irreversible activation of G proteins by GTP-gamma S. Verapamil (0.1-100 microM) also depressed the intracellular GTP-gamma S-induced K+ current. However, the magnitude of verapamil-depression of the K+ current in GTP-gamma S-loaded cells was significantly smaller than that in GTP-loaded cells at concentrations between 1 and 10 microM of the drug. From these results, it is suggested that verapamil may block not only the function of muscarinic ACh receptors but also of G proteins and/or the K+ channel itself and thereby depress the ACh-induced K+ current in isolated atrial myocytes. FAU - Ito, H AU - Ito H AD - 2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan. FAU - Takikawa, R AU - Takikawa R FAU - Kurachi, Y AU - Kurachi Y FAU - Sugimoto, T AU - Sugimoto T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Naunyn Schmiedebergs Arch Pharmacol JT - Naunyn-Schmiedeberg's archives of pharmacology JID - 0326264 RN - 0 (Parasympatholytics) RN - 0 (Potassium Channels) RN - 0 (Receptors, Cholinergic) RN - 0 (Receptors, Muscarinic) RN - 0 (Thionucleotides) RN - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate)) RN - 86-01-1 (Guanosine Triphosphate) RN - CJ0O37KU29 (Verapamil) RN - N9YNS0M02X (Acetylcholine) SB - IM MH - Acetylcholine/antagonists & inhibitors MH - Animals MH - Guanosine 5'-O-(3-Thiotriphosphate) MH - Guanosine Triphosphate/analogs & derivatives/pharmacology MH - Guinea Pigs MH - Heart/*drug effects MH - In Vitro Techniques MH - Myocardium/*cytology/metabolism MH - *Parasympatholytics MH - Potassium Channels/*drug effects MH - Receptors, Cholinergic/*drug effects MH - Receptors, Muscarinic/*drug effects MH - Thionucleotides/pharmacology MH - Verapamil/*pharmacology EDAT- 1989/01/01 00:00 MHDA- 1989/01/01 00:01 CRDT- 1989/01/01 00:00 PHST- 1989/01/01 00:00 [pubmed] PHST- 1989/01/01 00:01 [medline] PHST- 1989/01/01 00:00 [entrez] AID - 10.1007/BF00165150 [doi] PST - ppublish SO - Naunyn Schmiedebergs Arch Pharmacol. 1989 Jan-Feb;339(1-2):244-6. doi: 10.1007/BF00165150.