ELECTROTONIC INHIBITION AND ACTIVE FACILITATION OF EXCITABILITY IN VENTRICULAR MUSCLE

Citation
Jm. Davidenko et al., ELECTROTONIC INHIBITION AND ACTIVE FACILITATION OF EXCITABILITY IN VENTRICULAR MUSCLE, Journal of cardiovascular electrophysiology, 5(11), 1994, pp. 945-960
Citations number
34
Categorie Soggetti
Cardiac & Cardiovascular System
ISSN journal
10453873
Volume
5
Issue
11
Year of publication
1994
Pages
945 - 960
Database
ISI
SICI code
1045-3873(1994)5:11<945:EIAAFO>2.0.ZU;2-9
Abstract
Introduction: The effects of subthreshold electrical pulses on the res ponse to subsequent stimulation have been described previously in expe rimental animal studies as well as in the human heart. In addition, pr evious studies in cardiac Purkinje fibers have shown that diastolic ex citability may decrease after activity (active inhibition) and, to a l esser extent, following subthreshold responses (electrotonic inhibitio n). However, such dynamic changes in excitability have not been explor ed in isolated ventricular muscle, and it is uncertain whether similar phenomena may play any role in the activation patterns associated wit h propagation abnormalities in the myocardium. Methods and Results: Ex periments were performed in isolated sheep Purkinje fibers and papilla ry muscles, and in enzymatically dissociated guinea pig ventricular my ocytes. In all types of preparations introduction of a conditioning su bthreshold pulse between two suprathreshold pulses was followed by a t ransient decay in excitability (electrotonic inhibition). The degree o f inhibition was directly related to the amplitude and duration of the conditioning pulse and inversely related to the postconditioning inte rval. Yet, inhibition could be demonstrated long after (> 1 sec) the e nd of the conditioning pulse. Electrotonic inhibition was found at all diastolic intervals and did not depend on the presence of a previous action potential. In Purkinje fibers, conditioning action potentials l ed to active inhibition of subsequent responses. In contrast, in muscl e cells, such action potentials had a facilitating effect (active faci litation). Electrotonic inhibition and active facilitation were observ ed in both sheep ventricular muscle and guinea pig ventricular myocyte s. Accordingly, during repetitive stimulation with pulses of barely th reshold intensity, we observed: (1) bistability (i.e., with the same s timulating parameters, stimulus:response patterns were either 1:1 or 1 :0, depending on previous history), and (2) abrupt transitions between 1:1 and 1:0 (absence of intermediate Wenckebach-like patterns). Simul ations utilizing an ionic model of cardiac myocytes support the hypoth esis that electrotonic inhibition in well-polarized ventricular muscle is the result of partial activation of I-K following subthreshold pul ses. On the other hand, active facilitation may be the result of an ac tivity-induced decrease in the conductance of I-K1. Conclusion: Diasto lic excitability of well-polarized ventricular myocardium may be trans iently depressed following local responses and transiently enhanced fo llowing action potentials. On the other hand, diastolic excitability d ecreases during quiescence. Active facilitation and electrotonic inhib ition may have an important role in determining the dynamics of excita tion of the myocardium in the presence of propagation abnormalities.