Hyperpolarization is not responsible for the acetylcholine-induced negative chronotropic action in the presence of isoproterenol

Citation
M. Miura et al., Hyperpolarization is not responsible for the acetylcholine-induced negative chronotropic action in the presence of isoproterenol, BAS R CARD, 95(6), 2000, pp. 442-448
Citations number
23
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
BASIC RESEARCH IN CARDIOLOGY
ISSN journal
0300-8428 → ACNP
Volume
95
Issue
6
Year of publication
2000
Pages
442 - 448
Database
ISI
SICI code
0300-8428(200012)95:6<442:HINRFT>2.0.ZU;2-5
Abstract
It has been reported that acetylcholine hyperporarizes the maximum diastoli c potential of canine Purkinje fibers through a pathway involving a G prote in and induces a decrease in their automaticity. It is unclear, however, wh ether the negative chronotropic action of acetylcholine in the presence of beta -adrenegic stimulation is due to the hyperpolarization of the maximum diastolic potential or a decrease in the slope of phase 4 depolarization. W e used standard microelectrode techniques to study the negative chronotropi c mechanism of acetylcholine in the presence of isoproterenol in adult cani ne Purkinje fibers. Fibers were incubated for 24 hours in Tyrode's solution alone (n = 10) or plus pertussis toxin (n = 10), and then superfused with acetylcholine (10(-9) to 10(-4) M) in the presence of isoproterenol (10(-7) M). Acetylcholine in the presence of isoproterenol significantly decreased automaticity without hyperpolarization of the maximum diastolic potential, and decreased the slope of phase 4 depolarization. The effects of, acetylc holine on automaticity and the slope of phase 4 depolarization were attenua ted by pertussis toxin. The present findings indicate that the negative chr onotropic action of acetylcholine in the presence of isoproterenol is due t o the decrease in the slope of phase 4 depolarization through a pathway inv olving a pertussis toxin-sensitive G protein and that it is not the result of hyperpolarization of the maximum diastolic potential.