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Ionic basis of pacemaker generation in dog colonic smooth muscle
C Barajas-López1, A Den Hertog, J D Huizinga
1Intestinal Disease Research Unit, McMaster University, Hamilton, Ontario, Canada.
The Journal of Physiology
|September 1, 1989
Summary
Investigating the ionic basis of dog colon slow waves, this study found that while sodium and calcium ions are not essential for initiation, extracellular calcium is crucial. Slow wave generation involves cyclic membrane conductance changes, likely initiated by a potassium (K+) conductance blockade.
Area of Science:
- Gastrointestinal Physiology
- Electrophysiology
- Ion Transport
Background:
- Slow waves in the circular muscle of the dog colon are fundamental to gastrointestinal motility.
- The precise ionic mechanisms and conductances initiating these slow waves remain incompletely understood.
- Previous research suggested roles for Na+, Cl-, and Ca2+ in inward currents and K+ in outward currents.
Purpose of the Study:
- To elucidate the specific ionic conductances responsible for initiating slow waves in the dog colon.
- To investigate the roles of Na+, Cl-, Ca2+, and K+ ions in the generation and maintenance of colonic slow waves.
Main Methods:
- Intracellular electrical activity was measured using an Abe-Tomita-type voltage-clamp chamber.
- Ionic substitutions (Na+, Cl-) and channel blockers (tetrodotoxin, D600, CoCl2) were employed.
- Voltage-dependent properties were assessed through current-induced and ion-induced depolarization.
Main Results:
- Tetrodotoxin and Na+ omission did not abolish slow waves, indicating Na+ is not essential for initiation.
- Extracellular Ca2+ is indispensable for slow wave generation, though Ca2+ influx blockade (D600, CoCl2) only reduced amplitude and abolished plateau.
- High extracellular K+ shifted the voltage dependence of slow waves, suggesting a role for a voltage-dependent K+ conductance.
Conclusions:
- Slow waves are generated by cyclic membrane conductance changes dependent on extracellular Ca2+ and membrane potential.
- The data support the hypothesis that slow wave initiation involves the blockade of a K+ conductance.
- While Ca2+ influx is not strictly necessary, extracellular Ca2+ is vital for slow wave generation in the dog colon.