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 (50x 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 (20x 70 Hz, 200 ms duration, every 300 ms). However, using a long interval protocol (25x 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.
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 (50x 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 (20x 70 Hz, 200 ms duration, every 300 ms). However, using a long interval protocol (25x 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.
Authors: Jarkko J Ronkainen; Sandra L Hänninen; Topi Korhonen; Jussi T Koivumäki; Reka Skoumal; Sini Rautio; Veli-Pekka Ronkainen; Pasi Tavi Journal: J Physiol Date: 2011-03-28 Impact factor: 5.182
Authors: Johanna T Lanner; Dimitra K Georgiou; Aditya D Joshi; Susan L Hamilton Journal: Cold Spring Harb Perspect Biol Date: 2010-10-20 Impact factor: 10.005