Jm. Davidenko et al., ELECTROTONIC INHIBITION AND ACTIVE FACILITATION OF EXCITABILITY IN VENTRICULAR MUSCLE, Journal of cardiovascular electrophysiology, 5(11), 1994, pp. 945-960
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.