Differences in outward currents between neonatal and adult rabbit ventricular cells.
ABSTRACT In adult rabbit ventricular preparations, action potential duration is significantly increased when stimulation frequency is increased from 0.1 to 1.0 Hz. In neonatal preparations, a similar change in stimulation frequency produced no significant increase in action potential duration. To identify the ionic basis for this difference, we studied different outward currents in single myocytes from papillary muscle and from epicardial tissue of adult and neonatal rabbits. The densities of the outward currents in neonatal cells were about one-half of the current density in adult cells. The density of the voltage-activated transient outward current (I(to1)) was smaller in cells from papillary muscle than in cells from epicardium in adult and newborn rabbits. We found major differences in the kinetic behavior of I(to1) between adult and neonatal cells: 1) the rate of apparent inactivation was faster in neonatal cells, and 2) the recovery from inactivation was significantly faster in neonatal cells, with a time constant of 113 vs. 1,356 ms. We propose that this marked difference in the recovery from inactivation of I(to1) is the basis for the difference in frequency dependence of action potential duration.
Article: Electrophysiological and pharmacological correspondence between Kv4.2 current and rat cardiac transient outward current.[show abstract] [hide abstract]
ABSTRACT: The transient outward current (ITO) plays an important role in early repolarization and overall time course of the cardiac action potential. At least two K+ channel alpha-subunits cloned from cardiac tissue (Kv1.4 and Kv4.2) encode rapidly inactivating channels. The goal of this study was to determine functional and pharmacological properties of Kv4.2 expressed in mammalian cells, especially those that would differentiate between both isoforms in comparison to native ITO. Both Kv4.2 and Kv1.4 isoforms were stably expressed in mouse L-cell lines, and expressed currents were studied using whole-cell voltage clamp techniques. The expressed Kv4.2 currents displayed fast inactivation with a half-inactivation potential of -41 mV. Recovery from inactivation was rapid (tau recov = 160 ms at -90 mV) and strongly voltage-dependent. Flecainide (10 microM) had minimal effects on Kv1.4 currents, but reduced Kv4.2 peak current by 53% and increased the apparent rate of inactivation consistent with open channel block. Quinidine (10-20 microM) reduced the peak current and accelerated the apparent rate of inactivation in both isoforms. The Kv4.2 current displayed use-dependent unblock in the presence of 4-AP. The functional properties of Kv4.2, especially the flecainide sensitivity, resemble those of ITO in rat (and human) myocytes better than those of Kv1.4. These results provide the necessary functional support for the hypothesis that Kv4.2 is a major isoform contributing to cardiac ITO, consistent with independent biochemical and molecular evidence that indicates that Kv4.2 is readily detected in rat myocytes.Cardiovascular Research 04/1997; 33(3):540-7. · 6.06 Impact Factor
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ABSTRACT: The cloned Kv1.5 K+ channel displays similar kinetics and pharmacology to a delayed rectifier channel found in atrial myocytes. To determine whether the Kv1.5 isoform plays a role in the cardiac action potential, it is necessary to confirm the expression of this channel in cardiac myocytes. Using antibodies directed against two distinct channel epitopes, the Kv1.5 isoform was localized in human atrium and ventricle. Kv1.5 was highly localized at intercalated disk regions as determined by colocalization with connexin and N-cadherin specific antibodies. While both antichannel antibodies localized the Kv1.5 protein in cardiac myocytes, only the NH2-terminal antibodies stained vascular smooth muscle. The selective staining of vasculature by this antiserum suggests that epitope accessibility, and perhaps channel structure, varies between cardiac and vascular myocytes. Kv1.5 expression was localized less in newborn tissue, with punctate antibody staining dispersed on the myocyte surface. This increasing organization with age was similar to that observed for connexin. Future work will address whether altered K+ channel localization is associated with cardiac disease in addition to changing with development.Journal of Clinical Investigation 08/1995; 96(1):282-92. · 15.39 Impact Factor