Ionic basis of depressed automaticity and conduction by acetylcholine in rabbit AV node.
To investigate the ionic mechanisms underlying the negative chrono- and dromotropic effects of acetylcholine (ACh) on the atrioventricular (AV) node, experiments were carried out in rabbit AV node preparations with the use of double-microelectrode techniques. In current-clamp experiments (n = 6), 10(-6) M ACh hyperpolarized the resting membrane from -42.3 to -58.2 mV, decreased the specific membrane resistance from 2.54 to 1.27 k omega.cm2, decreased the space constant from 556 to 384 microns, and reduced the membrane time constant from 23.0 to 12.4 ms. Under voltage-clamp conditions, 10(-6) M ACh decreased the slow inward current by 11% and activated an ACh-sensitive outward K+ current (IACh). IACh possessed an inward rectifying property and exhibited a relaxation phenomenon with a time constant of 60-100 ms at a membrane potential of 0 to -80 mV. Its reversal potential varied with a slope factor of 56 mV per 10-fold increase in external K+ concentration. These results suggest that 1) IACh is selective for K+, 2) IACh inhibits phase 4 and phase 0 depolarizations and reduces the space constant for electronic current spread in the AV node, and 3) the negative chrono- and dromotropic actions caused by IACh may be augmented by the ACh-induced reduction in the slow inward current.
Nishimura
M
M
Cardiovascular Institute, Fujita Gakuen Health University School of Medicine, Aichi, Japan.
Habuchi
Y
Y
Hiromasa
S
S
Watanabe
Y
Y
D000109:Acetylcholine / Q000494:pharmacology*; D000465:Algorithms; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects*; D004553:Electric Conductivity; D004594:Electrophysiology; D006329:Heart Conduction System / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D014700:Verapamil; D000109:Acetylcholine; D011188:Potassium