Premium
Novel Oscillatory Mechanisms in the Cholinergic Control of Guinea Pig Sino‐Atrial Node Discharge
Author(s) -
VASSALLE MARIO,
NETT MICHAEL P.,
CATANZARO JOHN N.,
ROTA MARCELLO
Publication year - 2011
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.2010.01839.x
Subject(s) - cholinergic , hyperpolarization (physics) , carbachol , medicine , agonist , chronotropic , endocrinology , biophysics , inhibitory postsynaptic potential , heart rate , chemistry , receptor , biology , stereochemistry , blood pressure , nuclear magnetic resonance spectroscopy
Oscillatory Mechanisms in Sinus Node Cholinergic Control. Introduction: The role of the oscillatory after‐potential V os and pre‐potential ThV os in cholinergic control of discharge was studied in sino‐atrial node (SAN). Methods and Results: A microelectrode technique was used in isolated guinea‐pig SAN superfused in vitro in high [K + ] o to visualize V os and ThV os . The cholinergic agonist carbachol (CCh) decreased the amplitude and slope of V os and ThV os at a time when there was no increase in maximum diastolic potential. The slowing in SAN rate was due to slower and smaller ThV os that missed intermittently the threshold and occurred gradually later in diastole, but not to a decrease in the intrinsic rate of ThV os . Eventually, quiescence followed. Larger CCh concentrations quickly induced a hyperpolarization that altogether prevented the occurrence of oscillatory potentials. During CCh washout, ThV os reappeared and consistently reinitiated discharge. Lower [Ca 2+ ] o also decreased slopes and amplitude of V os and ThV os , thereby slowing and stopping SAN discharge, as CCh did. Overdrive temporarily offset the negative chronotropic effects of CCh and of low [Ca 2+ ] o. Cesium (a blocker of hyperpolarization‐activated current I f ) did not abolish CCh inhibitory effects on oscillatory potentials. Conclusions: The cholinergic agonist CCh: (1) slows SAN discharge by decreasing the amplitude of V os and ThV os , but not the rate of ThV os ; (2) can cause hyperpolarization that altogether suppresses the oscillatory potentials; (3) is mimicked in its effects by low [Ca 2+ ] o ; (4) is antagonized by procedures that increase cellular calcium; and (5) modifies the oscillatory potentials independently of I f . (J Cardiovasc Electrophysiol, Vol. 22, pp. 71‐80, January 2011)