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Regional differences in the negative inotropic effect of acetylcholine within the canine ventricle.
Author(s) -
Yang Z K,
Boyett M R,
Janvier N C,
McMorn S O,
Shui Z,
Karim F
Publication year - 1996
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1996.sp021346
Subject(s) - medicine , acetylcholine , ventricle , inotrope , cardiac transient outward potassium current , electrophysiology , chemistry , endocrinology , atropine , endocardium , patch clamp , cardiology
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.