Regional Differences In Action Potential Duration Research Articles

Spatial uniformity of action potentials indicates base-to-apex depolarization and repolarization of rainbow trout (Oncorhynchus mykiss) ventricle.

The spatial pattern of electrical activation is crucial for a full understanding of fish heart function. However, it remains unclear whether there is regional variation in action potential (AP) morphologies and underlying ion currents. Because the direction of depolarization and spatial differences in the durations of ventricular APs set limits to potential patterns of ventricular repolarization, we determined AP morphologies, underlying ion currents and ion channel expression in four different ventricular regions (spongy myocardium; and apex, base and middle of the compact myocardium), and correlated them with in vivo electrocardiograms (ECGs) in rainbow trout (Oncorhynchus mykiss). ECGs recorded from three leads indicated that the depolarization and repolarization of APs propagate from base to apex, and the main depolarization axis of the ventricle is between +90 and +120deg. AP shape was uniform across the whole ventricle, and little regional differences were found in the density of repolarizing K+ currents or depolarizing Ca2+ and Na+ currents and the underlying transcripts of ion channels, providing compelling evidence for the suggested excitation pattern. The spatial uniformity of AP durations and base-to-apex propagation of activation with a relatively slow velocity of propagation indicates no special ventricular conduction pathway in the trout ventricle such as the His-Purkinje system of mammalian hearts. The sequence of repolarization is solely determined by activation time without being affected by regional differences in AP duration.

Myocardial infarction in rat eliminates regional heterogeneity of AP profiles, I(to) K(+) currents, and [Ca(2+)](i) transients.

Transient outward K(+) current density (I(to)) has been shown to vary between different regions of the normal myocardium and to be reduced in heart disease. In this study, we measured regional changes in action potential duration (APD), I(to), and intracellular Ca(2+) concentration ([Ca(2+)](i)) transients of ventricular myocytes derived from the right ventricular free wall (RVW) and interventricular septum (SEP) 8 wk after myocardial infarction (MI). At +40 mV, I(to) density in sham-operated hearts was significantly higher (P < 0.01) in the RVW (15.0 +/- 0.8 pA/pF, n = 47) compared with the SEP (7.0 +/- 1.1 pA/pF, n = 18). After MI, I(to) density was not reduced in SEP myocytes but was reduced (P < 0.01) in RVW myocytes (8.7 +/- 1.0 pA/pF, n = 26) to levels indistinguishable from post-MI SEP myocytes. These changes in I(to) density correlated with Kv4.2 (but not Kv4.3) protein expression. By contrast, Kv1.4 expression was significantly higher in the RVW compared with the SEP and increased significantly after MI in RVW. APD measured at 50% or 90% repolarization was prolonged, whereas peak [Ca(2+)](i) transients amplitude was higher in the SEP compared with the RVW in sham myocytes. These regional differences in APD and [Ca(2+)](i) transients were eliminated by MI. Our results demonstrate that the significant regional differences in I(to) density, APD, and [Ca(2+)](i) between RVW and SEP are linked to a variation in Kv4.2 expression, which largely disappears after MI.

Effects of amphetamine on calcium and potassium currents in rat heart.

We used the patch-clamp technique to study the effects of amphetamine on the membrane currents responsible for rat cardiac action-potential duration. Amphetamine has no effect on the slow inward Ca2+ current (I(Ca)-L), the inwardly rectifying K+ current (I(K1) and the outward K+ delayed rectifier (I(K)) and sustained (I(SS)) currents. Amphetamine blocks the transient outward K+ current (I(to)) both in the open and in the rested state. The transient outward K+ current is largely responsible for action-potential repolarization and for the regional differences in action-potential duration in rat ventricle. Therefore, the reduction of the transient outward K+ current (I(to)) caused by amphetamine may facilitate the appearance of ventricular tachycardia and fibrillation, a reported cause of death in amphetamine users.

Regional differences in action potential characteristics and membrane currents of guinea-pig left ventricular myocytes.

Regional differences in action potential characteristics and membrane currents were investigated in subendocardial, midmyocardial and subepicardial myocytes isolated from the left ventricular free wall of guinea-pig hearts. Action potential duration (APD) was dependent on the region of origin of the myocytes (P < 0.01, ANOVA). Mean action potential duration at 90 % repolarization (APD90) was 237 +/- 8 ms in subendocardial (n = 30 myocytes), 251 +/- 7 ms in midmyocardial (n = 30) and 204 +/- 7 ms in subepicardial myocytes (n = 36). L-type calcium current (ICa) density and background potassium current (IK1) density were similar in the three regions studied. Delayed rectifier current (IK) was measured as deactivating tail current, elicited on repolarization back to -45 mV after 2 s step depolarizations to test potentials ranging from -10 to +80 mV. Mean IK density (after a step to +80 mV) was larger in subepicardial myocytes (1.59 +/- 0.16 pA pF-1, n = 16) than in either subendocardial (1.16 +/- 0.12 pA pF-1, n = 17) or midmyocardial (1. 13 +/- 0.11 pA pF-1, n = 21) myocytes (P < 0.05, ANOVA). The La3+-insensitive current (IKs) elicited on repolarization back to -45 mV after a 250 ms step depolarization to +60 mV was similar in the three regions studied. The La3+-sensitive tail current, (IKr) was greater in subepicardial (0.50 +/- 0.04 pA pF-1, n = 11) than in subendocardial (0.25 +/- 0.05 pA pF-1, n = 9) or in midmyocardial myocytes (0.38 +/- 0.05 pA pF-1, n = 11, P < 0.05, ANOVA). The contribution of a Na+ background current to regional differences in APD was assessed by application of 0.1 microM tetrodotoxin (TTX). TTX-induced shortening of APD90 was greater in subendocardial myocytes (35.7 +/- 7.1 %, n = 11) than in midmyocardial (15.7 +/- 3. 8 %, n = 10) and subepicardial (20.2 +/- 4.3 %, n = 11) myocytes (P < 0.05, ANOVA). Regional differences in action potential characteristics between subendocardial, midmyocardial, and subepicardial myocytes isolated from guinea-pig left ventricle are attributable, at least in part, to differences in IK and Na+-dependent currents.