Open AccessChanges in myoplasmic Ca 2+ during fatigue differ between FDB fibers, between glibenclamide‐exposed and Kir6.2 ‐/‐ fibers and are further modulated by verapamil
Author(s) -
Selvin David,
Renaud JeanMarc
Publication year - 2015
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12303
Subject(s) - glibenclamide , verapamil , kir6.2 , medicine , stimulation , endocrinology , chemistry , contraction (grammar) , muscle fatigue , biophysics , calcium , biology , biochemistry , diabetes mellitus , electromyography , protein subunit , physical medicine and rehabilitation , gene
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.