Regional differences in the negative inotropic effect of acetylcholine within the canine ventricle.
1. Regional differences in the effects of ACh on sub-epicardial, mid-wall and sub-endocardial cells of the dog left ventricle have been studied. 2. ACh produced a dose-dependent, atropine-sensitive negative inotropic effect that was greatest in sub-epicardial cells and small or absent in sub-endocardial cells. 3. In sub-epicardial (but not sub-endocardial) cells, ACh also resulted in a dose-dependent decrease in action potential duration. The inotropic effect of ACh on sub-epicardial cells was primarily the result of the decrease of action potential duration, because during trains of voltage clamp pulses the inotropic effect of ACh was reduced or abolished. At a holding potential of -80 mV, 10(-5)M ACh decreased L-type Ca2+ current by approximately 8% and this is thought to be responsible for the small inotropic effect during trains of pulses. 4. Although 4-AP, a blocker of the transient outward current (I(to)), abolished the "spike and dome' morphology of the sub-epicardial action potential, it had little or no effect on the actions of ACh on sub-epicardial cells. ACh had no effect on I(to) in sub-epicardial cells in voltage clamp experiments. 5. ACh activated a Ba(2+)-sensitive outward current (IK,ACh) in sub-epicardial cells, but little or no such current in sub-endocardial cells. In sub-epicardial cells, ACh also inhibited the inward rectifier current, IK,1. 6. It is concluded that in left ventricular sub-epicardial cells, ACh activates IK,ACh. This results in a shortening of the action potential and, therefore, a negative inotropic effect. In subendocardial cells, ACh activates little or no IK,ACh and, therefore, it has little or no negative inotropic effect. This may result from a regional variation in the expression of the muscarinic K+ channel.
Yang
Z K
ZK
Department of Physiology, University of Leeds, UK.
Boyett
M R
MR
Janvier
N C
NC
McMorn
S O
SO
Shui
Z
Z
Karim
F
F
D015761:4-Aminopyridine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism
D001464:Barium; D001285:Atropine; D015761:4-Aminopyridine; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium