Modulation of pacemaker activity of sinoatrial node cells by electrical load imposed by an atrial cell model.
To investigate the electrotonic modulation of sinoatrial (SA) node pacemaker activity by atrial muscle, single or multiple (2-7) SA node cells isolated from rabbit hearts were connected to a membrane model [resistance-capacitance (R-C) circuit] of an atrial cell through an external circuit that mimics the gap junctional conductance (Gc) between cells. When Gc was 0 nS (uncoupled conditions), all the preparations generated regular and stable spontaneous action potentials with a mean cycle length (SCL) of 263 +/- 45 ms (+/- SD, n = 35). Step increases of Gc were associated with a progressive prolongation of SCL. At sufficiently high values of Gc, the spontaneous activity became irregular and finally stopped. We defined the threshold Gc causing an appreciable SCL irregularity as the minimum Gc at which the ratio of SD to mean of SCL was > 0.3. The threshold Gc for a single SA node cell was calculated to be 0.58 nS. In the presence of acetylcholine (ACh; 0.05-0.2 microM), the coupling-induced inhibition of spontaneous activity was greatly increased, and the threshold Gc for a single SA node cell was decreased in a concentration-dependent manner. These findings show that the pacemaker activity of SA node cells is easily inhibited when the cells are coupled to a passive atrial cell model and the inhibition is amplified by ACh. Computer simulation using a modified Oxsoft HEART model indicates that the passive atrial cell model acts as a current sink, imposing a substantial outward current on the SA node cell, and ACh amplifies the effect by activating an additional outward current.
Watanabe
E I
EI
Department of Circulation, Nagoya University, Japan.
Honjo
H
H
Anno
T
T
Boyett
M R
MR
Kodama
I
I
Toyama
J
J
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D016275:Atrial Function / Q000502:physiology*; D002469:Cell Separation; D004594:Electrophysiology; D005260:Female; D008297:Male; D008955:Models, Cardiovascular; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D000109:Acetylcholine