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: Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.12303
• Languages: English
• ISSNs: 2051-817X

Abstract

<abstract abstract-type="main" id="phy212303-abs-0001"> <title>Abstract</title> <p>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<sup>2+</sup>]i in KATP‐channel‐deficient fibers. We measured changes in myoplasmic [Ca<sup>2+</sup>] ([Ca<sup>2+</sup>]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<sup>2+</sup>]i at the end than at the beginning of fatigue to fibers which eventually completely failed to release Ca<sup>2+</sup> upon stimulation. Compared to control conditions, KATP‐channel‐deficient fibers had a greater proportion of fiber with large decreases in tetanic [Ca<sup>2+</sup>]i, fade and complete failure to release Ca<sup>2+</sup> 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<sup>‐/‐</sup> and glibenclamide‐exposed muscle fibers. Verapamil significantly reduced unstimulated and tetanic [Ca<sup>2+</sup>]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<sup>2+</sup> load by reducing Ca<sup>2+</sup> influx through CaV1.1 channels between and during contractions.</p> </abstract>