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Activation of Ca 2+ ‐dependent protein kinase II during repeated contractions in single muscle fibres from mouse is dependent on the frequency of sarcoplasmic reticulum Ca 2+ release
Author(s) -
Aydin J.,
Korhonen T.,
Tavi P.,
Allen D. G.,
Westerblad H.,
Bruton J. D.
Publication year - 2007
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2007.01725.x
Subject(s) - chemistry , endoplasmic reticulum , stimulation , tetanic stimulation , biophysics , skeletal muscle , endocrinology , medicine , biochemistry , biology , receptor , long term potentiation
Aim: To investigate the importance and contribution of calmodulin‐dependent protein kinase II (CaMKII) activity on sarcoplasmic reticulum (SR) Ca 2+ ‐release in response to different work intensities in single, intact muscle fibres. Methods: CaMKII activity was blocked in single muscle fibres using either the inhibitory peptide AC3‐I or the pharmacological inhibitor KN‐93. The effect on tetanic force production and [Ca 2+ ] i was determined during work of different intensities. The activity of CaMKII was assessed by mathematical modelling. Results: Using a standard protocol to induce fatigue (50× 70 Hz, 350 ms duration, every 2 s) the number of stimuli needed to induce fatigue was decreased from 47 ± 3 contractions in control to 33 ± 3 with AC3‐I. KN‐93 was a more potent inhibitor, decreasing the number of contractions needed to induce fatigue to 15 ± 3. Tetanic [Ca 2+ ] i was 100 ± 11%, 97 ± 11% and 67 ± 11% at the end of stimulation in control, AC3‐I and KN‐93 respectively. A similar inhibition was obtained using a high intensity protocol (20× 70 Hz, 200 ms duration, every 300 ms). However, using a long interval protocol (25× 70 Hz, 350 ms duration, every 5 s) no change was observed in either tetanic [Ca 2+ ] i or force when inhibiting CaMKII. A mathematical model used to investigate the activation pattern of CaMKII suggests that there is a threshold of active CaMKII that has to be surpassed in order for CaMKII to affect SR Ca 2+ release. Conclusion: Our results show that CaMKII is crucial for maintaining proper SR Ca 2+ release and that this is regulated in a work intensity manner.