PMID- 2912601
OWN - NLM
STAT- MEDLINE
DCOM- 19890307
LR  - 20190706
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 64
IP  - 2
DP  - 1989 Feb
TI  - Anti-cholinergic effects of quinidine, disopyramide, and procainamide in isolated 
      atrial myocytes: mediation by different molecular mechanisms.
PG  - 297-303
AB  - Effects of quinidine, disopyramide, and procainamide on the acetylcholine 
      (ACh)-induced K+ channel 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 nonhydrolysable GTP analogue). In GTP-loaded cells, not only ACh but also 
      adenosine induced a specific K+ channel current via GTP-binding proteins (G) by 
      activating muscarinic ACh or adenosine receptors. Quinidine and disopyramide 
      depressed the ACh-induced K+ current quite effectively. Procainamide had a weak 
      inhibitory effect. Quinidine also depressed adenosine-induced K+ current, while 
      the effect of disopyramide on adenosine-induced current was much smaller than 
      that on ACh-induced current. In GTP-gamma S-loaded cells, the K+ channel was 
      uncoupled from the receptors and was activated irreversibly, probably due to 
      direct activation of G proteins by GTP-gamma S. Quinidine depressed the GTP-gamma 
      S-induced K+ current just as in the cases of ACh- and adenosine-induced currents 
      of GTP-loaded cells. Disopyramide had only a weak inhibitory effect and 
      procainamide showed no effect. From these results, it is strongly suggested that 
      the major mechanisms underlying the anti-cholinergic effects of quinidine, 
      disopyramide, and procainamide are different; quinidine may inhibit the 
      muscarinic K+ channel itself and/or G proteins, while disopyramide and high doses 
      of procainamide may mainly block functions of muscarinic ACh receptors in atrial 
      myocytes.
FAU - Nakajima, T
AU  - Nakajima T
AD  - 2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 
      Japan.
FAU - Kurachi, Y
AU  - Kurachi Y
FAU - Ito, H
AU  - Ito H
FAU - Takikawa, R
AU  - Takikawa R
FAU - Sugimoto, T
AU  - Sugimoto T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Parasympatholytics)
RN  - 0 (Potassium Channels)
RN  - 0 (Receptors, Muscarinic)
RN  - 0 (Receptors, Purinergic)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - GFO928U8MQ (Disopyramide)
RN  - ITX08688JL (Quinidine)
RN  - L39WTC366D (Procainamide)
SB  - IM
MH  - Animals
MH  - Biomechanical Phenomena
MH  - Disopyramide/*pharmacology
MH  - Guanosine Triphosphate/pharmacology
MH  - Guinea Pigs
MH  - Heart/*drug effects
MH  - In Vitro Techniques
MH  - Myocardium/cytology
MH  - Parasympatholytics/*pharmacology
MH  - Potassium Channels/drug effects
MH  - Procainamide/*pharmacology
MH  - Quinidine/*pharmacology
MH  - Receptors, Muscarinic/physiology
MH  - Receptors, Purinergic/physiology
EDAT- 1989/02/01 00:00
MHDA- 1989/02/01 00:01
CRDT- 1989/02/01 00:00
PHST- 1989/02/01 00:00 [pubmed]
PHST- 1989/02/01 00:01 [medline]
PHST- 1989/02/01 00:00 [entrez]
AID - 10.1161/01.res.64.2.297 [doi]
PST - ppublish
SO  - Circ Res. 1989 Feb;64(2):297-303. doi: 10.1161/01.res.64.2.297.