Changes in myoplasmic Ca2+ during fatigue differ between FDB fibers, between glibenclamide‐exposed and Kir6.2‐/‐ fibers and are further modulated by verapamil. Issue 3 (5th March 2015)

• Record Type: Journal Article
• Authors: Selvin, David; Renaud, Jean‐Marc
• Is Part Of: Physiological reports. Volume 3:Issue 3(2015:Mar.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2015-03-05
• Subjects: Ca2+ channel -- calcium -- fatigue -- Kir6.2 knockout; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.12303
• Languages: English
• ISSNs: 2051-817X

Abstract

Abstract: One objective of this study was to document how individual FDB muscle fibers depend on the myoprotection of KATP channels during fatigue. Verapamil, a CaV1.1 channel blocker, prevents large increases in unstimulated force during fatigue in KATP‐channel‐deficient muscles. A second objective was to determine if verapamil reduces unstimulated [Ca 2+ ]i in KATP‐channel‐deficient fibers. We measured changes in myoplasmic [Ca 2+ ] ([Ca 2+ ]i) using two KATP‐channel‐deficient models: (1) a pharmacological approach exposing fibers to glibenclamide, a channel blocker, and (2) a genetic approach using fibers from null mice for the Kir6.2 gene. Fatigue was elicited with one tetanic contraction every sec for 3 min. For all conditions, large differences in fatigue kinetics were observed from fibers which had greater tetanic [Ca 2+ ]i at the end than at the beginning of fatigue to fibers which eventually completely failed to release Ca 2+ upon stimulation. Compared to control conditions, KATP‐channel‐deficient fibers had a greater proportion of fiber with large decreases in tetanic [Ca 2+ ]i, fade and complete failure to release Ca 2+ upon stimulation. There was, however, a group of KATP‐channel‐deficient fibers that had similar fatigue kinetics to those of the most fatigue‐resistant control fibers. For the first time, differences in fatigue kinetics were observed between Kir6.2 ‐/‐ and glibenclamide‐exposed muscle fibers. Verapamil significantly reduced unstimulated and tetanic [Ca 2+ ]i. It is concluded that not all fibers are dependent on the myoprotection of KATP channels and that the decrease in unstimulated force by verapamil reported in a previous studies in glibenclamide‐exposed fibers is due to a reduction in Ca 2+ load by reducing Ca 2+ influx through CaV1.1 channels between and during contractions. Abstract : This study is the first to demonstrate the large variability in fatigue kinetics between mouse fibers at the physiological temperature of 37°C. It also documents that not all fibers are dependent on the myoprotective effect of KATP channel during fatigue. Finally, it demonstrates that the large increase in unstimulated force during fatigue in KATP channel is related to a calcium load due to an influx of calcium between and during contractions.