© 1997 American Heart Association, Inc.
Articles |
Alterations of Na+ Currents in Myocytes From Epicardial Border Zone of the Infarcted Heart
A Possible Ionic Mechanism for Reduced Excitability and Postrepolarization Refractoriness
From the Department of Pharmacology, Columbia University, New York, NY.
Correspondence to Penelope A. Boyden, Department of Pharmacology, Columbia College of Physicians and Surgeons, 630 West 168th St, New York NY 10032. E-mail pab4{at}columbia.edu
Abstract Previously, we have shown abnormalities in
max and in the recovery of max in
myocytes dispersed from the epicardial border zone (EBZ) of the 5-day
infarcted canine heart (myocytes from the EBZ [IZs]). Thus, we sought
to determine the characteristics of the whole-cell Na+
current (INa) in IZs and compare them with the
INa of cells from noninfarcted hearts (myocytes
from noninfarcted epicardium [NZs]). INa was
recorded using patch-clamp techniques under conditions that
eliminated contaminating currents and controlled
INa for measurement (19°C, 5 mmol/L
[Na+]o). Peak INa
density (at -25 mV) was significantly reduced in IZs (4.9±0.44 pA/pF,
n=36) versus NZs (12.8±0.55 pA/pF, n=54; P<.001), yet the
half-maximal activation voltage (V0.5), time course of
decay, and time to peak INa were no different.
However, in IZs, V0.5 of the availability curve
(I/Imax curve) was shifted
significantly in the hyperpolarizing direction (-80.2±0.48 mV in NZs
[n=45] versus -83.9±0.59 mV in IZs [n=27], P<.01).
Inactivation of INa directly from a depolarized
prepotential (-60 mV) was significantly accelerated in IZs versus NZs
(fast and slow time constants [
1 and 2,
respectively] were as follows: NZs [n=28],
1=71.5±5.6 ms and 2=243.7±17.1 ms; IZs
[n=21], 1=36.3±2.4 ms and 2=153±11.3
ms; P<.001). Recovery of INa from
inactivation was dependent on the holding potential (VH) in
both cell types but was significantly slower in IZs. At
VH=-90 mV, INa recovery had a lag
in 18 (82%) of 22 IZs (with a 17.6±1.5-ms lag) versus 2 (9%) of 22
NZs (with 5.9- and 8.7-ms lags); at VH=-100 mV,
1=60.9±2.6 ms and 2=352.8±28.1 ms in
NZs (n=41) versus 1=76.3±4.8 ms and
2=464.4±47.2 ms in IZs (n=26) (P<.002 and
P<.03, respectively); at VH=-110 mV,
1=33.4±1.8 ms and 2=293.5±33.6 ms in
NZs (n=21) versus 1=44.3±2.9 ms and
2=388.4±38 ms in IZs (n=18) (P<.002 and
P<.07, respectively). In sum, INa is
reduced, and its kinetics are altered in IZs. These changes may
underlie the altered excitability and postrepolarization
refractoriness of the ventricular fibers of the EBZ,
thus contributing to reentrant arrhythmias in the infarcted
heart.
Key Words: Na+ current • ion channel • ventricular myocyte • myocardial infarction • epicardial border zone
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