Characterization of L-type calcium channel activity in atrioventricular nodal myocytes from rats with streptozotocin-induced Diabetes mellitus

Yuill, Kathryn H; Al Kury, Lina T; Howarth, Frank Christopher

Abstract

© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. Cardiovascular complications are common in patients with Diabetes mellitus (DM). In addition to changes in cardiac muscle inotropy, electrical abnormalities are also commonly observed in these patients. We have previously shown that spontaneous cellular electrical activity is altered in atrioventricular nodal (AVN) myocytes, isolated from the streptozotocin (STZ) rat model of type-1 DM. In this study, utilizing the same model, we have characterized the changes in L-type calcium channel activity in single AVN myocytes. Ionic currents were recorded from AVN myocytes isolated from the hearts of control rats and from those with STZ-induced diabetes. Patch-clamp recordings were used to assess the changes in cellular electrical activity in individual myocytes. Type-1 DM significantly altered the cellular characteristics of L-type calcium current. A reduction in peak ICaL density was observed, with no corresponding changes in the activation parameters of the current. L-type calcium channel current also exhibited faster time-dependent inactivation in AVN myocytes from diabetic rats. A negative shift in the voltage dependence of inactivation was also evident, and a slowing of restitution parameters. These findings demonstrate that experimentally induced type-1 DM significantly alters AVN L-type calcium channel cellular electrophysiology. These changes in ion channel activity may contribute to the abnormalities in cardiac electrical function that are associated with high mortality levels in patients with DM.

Citation

Yuill, K. H., Al Kury, L. T., & Howarth, F. C. (2015). Characterization of L-type calcium channel activity in atrioventricular nodal myocytes from rats with streptozotocin-induced Diabetes mellitus. Physiological Reports, 3(11), Article e12632. https://doi.org/10.14814/phy2.12632

• Journal Article Type: Article
• Acceptance Date: Oct 26, 2015
• Online Publication Date: Nov 24, 2015
• Publication Date: Nov 1, 2015
• Deposit Date: Jul 2, 2019
• Publicly Available Date: Jul 2, 2019
• Journal: Physiological Reports
• Electronic ISSN: 2051-817X
• Publisher: Wiley Open Access
• Peer Reviewed: Peer Reviewed
• Volume: 3
• Issue: 11
• Article Number: e12632
• DOI: https://doi.org/10.14814/phy2.12632
• Keywords: atrioventricular node, calcium channel, cardiac, diabetes, ion channel
• Public URL: https://uwe-repository.worktribe.com/output/1467467
• Publisher URL: https://doi.org/10.14814/phy2.12632