Relationship between transient outward K⁺ current and Ca²⁺ influx in rat cardiac myocytes of endo‐ and epicardial origin

Abstract

Inotropic effects of electric currents. I. Positive and negative effects of constant electric currents or current pulses applied during cardiac action potentials. II. Hypotheses: calcium movements, excitationcontraction coupling and inotropic effects. Circulation Research 24, 409-445.

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

“…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).…”

“…These findings suggest that variations in I to underlie regional differences in myocardial contractility. Because the density of I to in RVW rat myocytes is not significantly different from those recorded in epicardial myocytes from the left ventricle (16.2 Ϯ 1.9 pA/pF at ϩ40 mV, P ϭ 0.5), our results can help explain the greater contractile force generated and larger contribution to pressure development by endocardial versus epicardial regions of the left ventricle (19,54). Differences in peak magnitudes of the [Ca 2ϩ ] i transients between the groups might also conceivably be related to variations in I Ca,L density independent of changes in APD.…”

“…Indeed, APD prolongation in rat myocytes is associated with increased [Ca 2ϩ ] i transient amplitudes (7,10,30,54), particularly when APD prolongation is caused by reductions in I to (46,54). The link between changes in I to density and [Ca 2ϩ ] i in rat myocytes can be traced to the profound impact that the relatively fast activating and inactivating I to has on the early repolarization period when I Ca,L are also prominent (30,46,54). In our studies, peak [Ca 2ϩ ] i was much lower in RVW versus SEP myocytes, which correlated strongly with higher I to densities and shorter APDs.…”

“…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 hypertrophied (10, 30) rat ventricular myocytes.In this study, we examined the regional changes in APD, I to density, and [Ca 2ϩ ] i transient magnitude and MI and correlated these differences with the expression of K ϩ channel genes encoding for I to (i.e., Kv1.4, Kv4.2, and Kv4.3). Our results show that gradients in APD, I to density, Kv4.2 expression, and peak [Ca 2ϩ ] i exist between the right ventricular free wall (RVW) and interventricular septum (SEP), and these differences are largely eliminated after myocardial infarction (MI).…”

“…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 hypertrophied (10, 30) rat ventricular myocytes.…”