B. Szabo et al., ROLE OF NA-INDUCED EARLY AFTERDEPOLARIZATIONS IN PURKINJE-FIBERS(CA2+EXCHANGE CURRENT IN CS+), Journal of cardiovascular electrophysiology, 5(11), 1994, pp. 933-944
Introduction: The ionic mechanisms for early afterdepolarizations (EAD
s) have not been fully clarified. It has been suggested that L-type Ca
2+ current (I-CaL) is the primary current generating EADs that occur n
ear the plateau level (E-EADs) of the membrane potential (Vm) when I-C
aL is enhanced. The purpose of these studies was to determine accurate
ly the range of Vm at which EADs occur in Purkinje fibers with K+ curr
ents blocked by Cs+ and to investigate the importance of Na+:Ca2+ exch
ange current (I-Na:Ca) as opposed to I-CaL and other currents in the g
eneration of EADs occurring later during repolarization (L-EADs). Meth
ods and Results: Shortened Purkinje strands from dogs and guinea pigs
were superfused with physiologic solution containing Cs+ (3.6 mM) and
a low [K+](0) (3.0 or 2.0 mM) to induce EADs. The Vm of origin of EADs
and their evolution were measured with the aid of phase plane plots o
f the rate of repolarization against Vm. L-EADs occurred over a wide r
ange of Vm (-35 to -90 mV), generally more negative in guinea pig than
in dog. Elevation of [Ca2+](0) from 1.8 to 3.6 mM suppressed L-EADs w
ithin a few cycles, and they returned with continued exposure. After r
epeated exposures to high [Ca2+](0) L-EADs migrated toward less negati
ve Vm when [Ca2+](0) was reestablished to 1.8 mM in the presence of Cs
+. Reduction of [Na+](0) from 147.5 to 112.5 mM by substitution with L
i+ or sucrose also rapidly depressed L-EADs. Conclusions: The observat
ion of Cs+-induced L-EADs over a wide range of Vm indicates that there
is not a single inward gated current as a common ionic mechanism for
L-EADs but does not exclude an important role for I-Na:Ca, which can o
perate over a wide range of Vm. The rapid suppression of L-EADs with e
levated [Ca2+](0) and reduced [Na+](0) and the migration of EADs to mo
re positive Vm after exposures to high [Ca2+](0) are compatible with I
-Na:Ca as the major charge carrier for L-EADs.