Novel oscillatory mechanisms in the cholinergic control of Guinea pig sino-atrial node discharge.
Oscillatory Mechanisms in Sinus Node Cholinergic Control.


BACKGROUND
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).


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) .
Vassalle
Mario
M
Department of Physiology and Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, USA. mario.vassalle@downstate.edu
Nett
Michael P
MP
Catanzaro
John N
JN
Rota
Marcello
M
D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D011950:Receptors, Cholinergic / Q000378:metabolism*; D012849:Sinoatrial Node / Q000502:physiology*
D011950:Receptors, Cholinergic; D000109:Acetylcholine