THE MECHANISMS OF CARDIAC ARRHYTHMIA

Abstract

Recent work has introduced two new techniques to cardiac electrophysiology:
1. Isolation of single cardiac cells using enzymatic separation.
This technique permits much faster and more reliable voltage clamp experiments to be perfomed.
2. Patch recording of single ionic channels and of single cell ionic currents.
These techniques have been used to show that the calcium current is activated and inactivated much more quickly than was shown by previous work on multicellular preparations. This leaves open the question what carries the slower components of inward current.
It has been shown that there are three possible mechanisms:
(i) There exists more than one type of calcium channel. Some channels may show slower kinetics.
(ii) Intracellular calcium may activate current carried by the sodiumcalcium exchange process.
(iii) Intracellular calcium may activate non-specific cation channels.
Evidence will be presented for mechanisms (i) and (ii)
These new results have been incorporated into a very extensive computer model: It will be shown that this model not only succeeds in reproducing normal electrical activity but is also capable of reproducing arrhythmias generated in the following circumstances:
(a) Block of the Na-K pump by cardiac glycosides or by low K.
(b) Stimulation with a current pulse during repolarization.
(c) Low extracellular calcium concentrations.