Differences in regional distribution of K+ current densities in rat ventricle

Casis, Óscar; Iriarte, Marian; Gallego, Mónica; Sánchez-Chapula, José A.

doi:10.1016/s0024-3205(98)00287-2

Cited by 59 publications

(59 citation statements)

References 19 publications

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“…However, in the rat heart, the I to density is identical between RVW myocytes and left ventricular epicardial myocytes (R. Kaprielian and P. H. Backx, unpublished observations), as reported previously (14), whereas the I to density in SEP myocytes is similar to that observed in left ventricular endocardial myocytes (11,49,55,61). Moreover, a recent study (55) in the rat aortic stenosis model showed a similar pattern of electrical changes between the epicardium and endocardium of the left ventricle between the epicardial RVW and the endocardial septum.…”

Section: Discussionsupporting

confidence: 83%

“…Clearly, variations in other currents could also conceivably contribute to regional differences in APD. However, in this study, no detectable differences were observed between RVW and SEP myocytes in I sus , I K1 , or I Ca,L , suggesting these currents are not responsible for APD heterogeneity as previously reported (2,14). Nevertheless, possible differences in other currents to the regional variations in APD cannot be ruled out.…”

Section: Discussionsupporting

confidence: 46%

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Myocardial infarction in rat eliminates regional heterogeneity of AP profiles,I_toK⁺currents, and [Ca²⁺]_itransients

Kaprielian

Sah

Nguyen

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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(Ito) 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 2ϩ concentration ([Ca 2ϩ ]i) transients of ventricular myocytes derived from the right ventricular free wall (RVW) and interventricular septum (SEP) 8 wk after myocardial infarction (MI). At ϩ40 mV, I to density in sham-operated hearts was significantly higher (P Ͻ 0.01) in the RVW (15.0 Ϯ 0.8 pA/pF, n ϭ 47) compared with the SEP (7.0 Ϯ 1.1 pA/pF, n ϭ 18). After MI, I to density was not reduced in SEP myocytes but was reduced (P Ͻ 0.01) in RVW myocytes (8.7 Ϯ 1.0 pA/pF, n ϭ 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 2ϩ ]i transients amplitude was higher in the SEP compared with the RVW in sham myocytes. These regional differences in APD and [Ca 2ϩ ]i transients were eliminated by MI. Our results demonstrate that the significant regional differences in I to density, APD, and [Ca 2ϩ ]i between RVW and SEP are linked to a variation in Kv4.2 expression, which largely disappears after MI. right ventricle; septum; heart disease; contraction THERE ARE MARKED DIFFERENCES in the action potential duration (APD) in different regions of the mammalian ventricle (4,15,18,39,58). This electrical heterogeneity in normal myocardium correlates with regional differences in the Ca 2ϩ -independent transient outward K ϩ current density (I to ) (5,15,18,34,35,43) as well as in gene expression of K ϩ channels (8,16,58). APD prolongation and reductions in I to density occur in rat heart after left anterior descending coronary artery ligation (2, 43, 58), aortic banding (5, 22, 55), as well as after treatment with either catecholamine (11) or monocrotaline (32, 33). Depending on the model, the extent of I to density changes in disease may not be uniform throughout the ventricle (2, 5, 11, 22, 55), thereby leading to possible losses of electrical heterogeneity and increased susceptibility to arrhythmias (3).Aside from electrical heterogeneity, regional differences in other myocardial properties also exist. For example, systolic intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) is higher in the endocardium than in the epicardium (19,54), consistent with the notion that the endocardium may play a more important role in contraction compared with the epicardium. The underlying basis for the regional differences in contraction is currently unknown but may be related to a heterogeneous transmural expression of Ca 2ϩ handling proteins (26, 31). Alternatively, APD might also play a key role because the action potential profile is an important determinant of the inotropic state of the heart in both normal (7,42,54) and hy...

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 46%

Myocardial infarction in rat eliminates regional heterogeneity of AP profiles,I_toK⁺currents, and [Ca²⁺]_itransients

Kaprielian

Sah

Nguyen

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…From our results, we can see that there are no regional differences in the inactivation characteristics of I to and I K in control cells, as previously described in rat [21] and rabbit ventricles [24]. Half inactivation voltages and slope factors are not changed by Type I diabetes on I to inactivation [13].…”

Section: Discussionsupporting

confidence: 81%

“…To test this possibility, we studied the inactivation characteristics of these currents using a typical two pulse protocol, with a 10 s prepulse ranging from ±120 to 0 mV, followed by a 50 ms test pulse to + 50 mV. Peak current amplitudes at + 50 mV were plotted against the voltage of the prepulse and fitted to the equation: The first and second components correspond to I K and I to inactivation, and ªRº corresponds to the noninactivating I ss [15,21]. Figure 6 shows the change in the proportion of relative amplitudes with respect to the others, although there was no change in half-inactivation voltages (V h1 and V h2 ) or in slope factor (S 1 and S 2 ) ( Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…The regional disparity of K + currents is responsible for some of the well-known differences in the duration of the rat ventricular action potentials [10,11,21]. Therefore, the relative participation of the currents to the repolarisation process could differ in the different regions, thus, I to participation in control hearts is in RV greater than in EpiALV and in EpiALV greater than in EndoBLV.…”

Section: Discussionmentioning

confidence: 99%

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Effects of diabetic cardiomyopathy on regional electrophysiologic characteristics of rat ventricle

Casis

Gallego

Iriarte³

et al. 2000

Diabetologia

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The electrocardiogram of diabetic patients shows a series of deviations from normal patterns, most of which involve the QT interval and the T wave. The QT interval is longer in patients with diabetes mellitus than in normal people [1]. Diabetic patients show a corrected QT interval (QTc), measured using Bazett's formula, longer than 0.44 s [2,3]. Using Holter ECG monitoring, the appearance of ventricular late potentials is more frequent in patients with Type I (insulin-dependent) diabetes mellitus than in healthy people, and even more frequent in patients with Type II (non-insulin-dependent) diabetes mellitus [4,5]. Nearly all these changes are related to repolarisation. The QRS complex lasts longer in diabetic patients than in control subjects, suggesting intracardiac conduction disorders, but this type of change has only been described in children [6].Various studies report a lengthening of the duration of the rat ventricular action potential (APD) stemming from diabetic cardiomyopathy as a possible cause of these changes [7±9]. None took into account, however, the regional variability in the duration of the action potential under control conditions [10,11]. Various reports pointed to a lowering of the transient outward current, I to [9,12,13] and, to a lesser extent, the delayed rectifying outward current, I K [9,12], as the main cause of the lengthening of APD. Initial studies did not take into account regional variations in the distribution of the repolarising outward Diabetologia (2000) Abstract Aims/hypothesis. To identify the possible causes of the lengthening of the action potential duration described in patients affected by diabetes mellitus. Methods. We studied the effects of streptozotocininduced diabetes on the current density of the repolarising potassium currents I to , I K , I ss and I K1 in enzymatically isolated myocytes from three different regions of rat heart: total right ventricle, subepicardium at the apex of the left ventricle and subendocardium at the base of the left ventricle. Results. No changes in I K1 were found due to diabetes, but there was a uniform decrease in I to (50 %) and I ss (40 %) current densities in the three regions.In contrast, I K diminished unevenly, with the greatest decrease in the subendocardium at the base of the left ventricle (48 %), followed by the subepicardium at the apex of the left ventricle (32 %) and right ventricle (10 %). Conclusion/interpretation. These findings suggest the existence of regional differences in ion channel expression associated with diabetes. The decrease of these repolarising currents could account for the lengthening of action potential and the consequent change in the Q-T interval of the ECG observed in diabetic rats. [Diabetologia (2000)

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Regulation of cardiac transient outward potassium current by norepinephrine in normal and diabetic rats

Gallego

Casis

2001

Diabetes Metabolism Res

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Differences in regional distribution of K+ current densities in rat ventricle

Cited by 59 publications

References 19 publications

Myocardial infarction in rat eliminates regional heterogeneity of AP profiles,I_toK⁺currents, and [Ca²⁺]_itransients

Myocardial infarction in rat eliminates regional heterogeneity of AP profiles,I_toK⁺currents, and [Ca²⁺]_itransients

Effects of diabetic cardiomyopathy on regional electrophysiologic characteristics of rat ventricle

Regulation of cardiac transient outward potassium current by norepinephrine in normal and diabetic rats

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Differences in regional distribution of K+ current densities in rat ventricle

Cited by 59 publications

References 19 publications

Myocardial infarction in rat eliminates regional heterogeneity of AP profiles,ItoK+currents, and [Ca2+]itransients

Myocardial infarction in rat eliminates regional heterogeneity of AP profiles,ItoK+currents, and [Ca2+]itransients

Effects of diabetic cardiomyopathy on regional electrophysiologic characteristics of rat ventricle

Regulation of cardiac transient outward potassium current by norepinephrine in normal and diabetic rats

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Product

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Myocardial infarction in rat eliminates regional heterogeneity of AP profiles,I_toK⁺currents, and [Ca²⁺]_itransients

Myocardial infarction in rat eliminates regional heterogeneity of AP profiles,I_toK⁺currents, and [Ca²⁺]_itransients