Abstract
<h3>Background</h3> In contrast to the consensus notion that cardiac ATP-sensitive potassium (K<sub>ATP</sub>) channels are composed of Kir6.2 as the pore-forming subunit and SUR2A as the regulatory subunit, recent studies have revealed that rodent atrial K<sub>ATP</sub> channels are primarily regulated by SUR1 subunit. In addition, a gain-of-function mutation of Kir6.1 subunit has recently been linked to a form of Brugada syndrome. Heterogeneity of K<sub>ATP</sub> channels within and between heart chambers may differentially predispose certain myocytes to action potential (AP) shortening. <h3>Methods</h3> To assess the heterogeneity of cardiac K<sub>ATP</sub> channels in large animals, whole-cell and excised patch-clamp recordings were performed on myocytes isolated from dog atrium, ventricular epicardium (Epi), mid myocardium (Mid), and endocardium (Endo). To measure the consequences of K<sub>ATP</sub> channel opening on dog myocytes, dynamic current clamp was applied via a custom analog circuit to simulate a progressively increasing linear K<sup>+</sup> conductance. <h3>Results</h3> Mean K<sub>ATP</sub> conductance (activated by metabolic inhibitors) did not differ significantly between chambers (49 ± 9 pA/pF in atrium vs 43 ± 5 pA/pF in ventricle); however, within the ventricle the current was smallest in Endo (29 ± 5 pA/pF) vs Epi (53 ± 11 pA/pF, <i>P</i> <.05) and Mid (46 ± 10 pA/pF, <i>P</i> <.05). Pinacidil-activated (SUR2A-specific) current was large in both atrium (40 ± 4 pA/pF) and ventricle (47 ± 7 pA/pF). Diazoxide-activated (SUR1-specific) current in atrium (13 ± 6 pA/pF) was significantly larger than in ventricle (3 ± 2 pA/pF, <i>P</i> <.05). In current clamp, myocytes with longer action potential duration (APD) (Mid) were more susceptible to injected "K<sub>ATP</sub>" current, a result that is reproduced <i>in silico</i> using a second-generation canine ventricular AP model to simulate Epi, Mid, and Endo (HRd2010). The results indicate that increased shortening is caused by replenishment of repolarizing current that is otherwise lacking in cells with long APDs. <h3>Conclusions</h3> If similarly activated, the heterogeneous makeup of K<sub>ATP</sub> channels between and within heart chambers is likely to cause proarrhythmic dispersion of repolarization; however, the enhanced shortening of long APDs by K<sub>ATP</sub> current would tend to reduce dispersion and may consequently be protective.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
