Localization of the Kv1.5 K+ channel protein in explanted cardiac tissue.

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. (J. Clin. Invest. 1995. 96:282-292.)

Cortactin Is Required for N-cadherin Regulation of Kv1.5 Channel Function

“…Although Kv1.5 staining in WT adult ventricular myocytes could be seen extensively throughout the cell surface and at Z-lines, it was also localized prominently in the ICD (Fig. 4A), as reported previously (27,28). In contrast, in N-cad CKO ventricular myocytes Kv1.5 appeared absent from the ICD (Fig.…”

“…Several channels and transporters have been found to be largely localized to the intercalated disc, including Kv1.5 (27). The Na v 1.5 sodium channel resident at the intercalated disc has been suggested to play a role in initiation and conduction of the action potential (40,41).…”

Cytoskeletal Basis of Ion Channel Function in Cardiac Muscle

“…The latter is expressed in human cardiomyocytes and localizes to the intercalated disk of the cardiomyocyte in association with connexin 43 and N-cadherin. 21 In their experiments, Maruoka et al treated HEK293 cells stably expressing Kv1.5 with cytochalasin D, which led to a massive increase in ionic and gating I K+ currents. 20 The observed phenomenon was entirely prevented by pre-incubation with phalloidin, an F-actin stabilizing agent.…”

Do Alterations in Intercellular Coupling Play a Role in Cardiac Contractile Dysfunction?

“…Other mechanisms (both direct and indirect) could link development of derangements in passive electrical properties and the development of alterations in active electrical properties, excitationcontraction coupling, and contractile performance. For example, recent evidence indicates that some voltage-sensitive potassium channels, 16 voltage-gated sodium channels, 17 and inositol trisphosphate receptors 18 are concentrated at sites of intercellular junctions. Alterations in the number or distribution of gap junctions could affect the distribution and possibly even the function of sarcolemmal ion channels or the functions of Ca 2ϩ regulatory proteins in the sarcoplasmic reticulum that would affect excitation-contraction coupling and mechanical function.…”