Effects of tissue geometry on initiation of a cardiac action potential.
We used rabbit ventricular papillary muscles and isolated rabbit ventricular muscle cells to compare the effects of a decrease in cardiac excitability. For the papillary muscles, we defined tissue excitability as the inverse of the current required to initiate a propagated action potential from a local stimulus. For the isolated cells, we defined cellular excitability as the inverse of the current required to initiate a membrane action potential. For papillary muscles, lidocaine with elevated extracellular K+ concentration ([K+]o) decreased maximum rate of rise of membrane potential (Vmax), decreased conduction velocity, and strongly decreased tissue excitability. For the isolated cells, lidocaine with elevated [K+]o decreased Vmax but had little effect on cellular excitability. We interpret our results on the differences of effect on tissue excitability vs. cellular excitability as a consequence of the syncytial nature of the papillary muscle. The cell-to-cell electrical connections produce an electrical load on the locally stimulated region. This electrical load makes the tissue excitability dependent on the amount of inward current that the locally excited cells and the surrounding cells can generate. We simulated these phenomena with numerical solutions of action potential initiation in an isopotential cell compared with a two-dimensional disk of excitable tissue. The simulation results recreate the basic experimental observation that the sensitivity of the current threshold to agents that lower inward current is markedly larger for multidimensional current flow from a source compared with an isopotential system.
Joyner
R W
RW
Todd Franklin Cardiac Research Laboratory, Department of Pediatrics, Emory University, Atlanta, Georgia 30322.
Ramza
B M
BM
Tan
R C
RC
Matsuda
J
J
Do
T T
TT
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D008433:Mathematics; D008564:Membrane Potentials; D008962:Models, Theoretical; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors; D016276:Ventricular Function
D011189:Potassium Chloride; D008012:Lidocaine