PURPOSE: Malignant hyperthermia (MH) results from disordered calcium (Ca(2+)) homeostasis in skeletal muscle during general anesthesia. Although Ca(2+) channel blockers may be given to treat the tachycardia and circulatory instability, coadministration of Ca(2+) channel blockers and dantrolene is contraindicated during MH crisis. We evaluated the effect of Ca(2+) channel blockers on Ca(2+) homeostasis and their interactions with dantrolene in human skeletal muscle. METHODS: Human skeletal muscle samples were obtained by biopsy and divided into two groups according to the results of the Ca(2+)-induced Ca(2+) release rate test. Differentiated myotubes were labeled with Fura-2, and changes in the 340/380-nm ratio were used to calculate changes in Ca(2+) concentration following nifedipine treatment in the absence or presence of dantrolene. RESULTS: Nifedipine induced a transient increase in the intracellular Ca(2+) concentration ([Ca(2+)](i)) in a dose-dependent manner. The half-maximal concentration (EC(50)) for nifedipine was 0.718 ± 0.329 μM in the accelerated group and 1.389 ± 0.482 μM in the nonaccelerated group (P = 0.009). The addition of 50 μM dantrolene attenuated by 15.4% the increase in [Ca(2+)](i) caused by the 0.5 μM nifedipine. CONCLUSION: Ca(2+) channel blockers led to increased [Ca(2+)](i) in human skeletal muscle cells. The increase is thus scarcely affected by dantrolene treatment. Data provide a greater physiologic basis for avoiding the use of Ca(2+) channel blockers during MH crisis.
PURPOSE:Malignant hyperthermia (MH) results from disorderedcalcium (Ca(2+)) homeostasis in skeletal muscle during general anesthesia. Although Ca(2+) channel blockers may be given to treat the tachycardia and circulatory instability, coadministration of Ca(2+) channel blockers and dantrolene is contraindicated during MH crisis. We evaluated the effect of Ca(2+) channel blockers on Ca(2+) homeostasis and their interactions with dantrolene in human skeletal muscle. METHODS:Human skeletal muscle samples were obtained by biopsy and divided into two groups according to the results of the Ca(2+)-induced Ca(2+) release rate test. Differentiated myotubes were labeled with Fura-2, and changes in the 340/380-nm ratio were used to calculate changes in Ca(2+) concentration following nifedipine treatment in the absence or presence of dantrolene. RESULTS:Nifedipine induced a transient increase in the intracellular Ca(2+) concentration ([Ca(2+)](i)) in a dose-dependent manner. The half-maximal concentration (EC(50)) for nifedipine was 0.718 ± 0.329 μM in the accelerated group and 1.389 ± 0.482 μM in the nonaccelerated group (P = 0.009). The addition of 50 μM dantrolene attenuated by 15.4% the increase in [Ca(2+)](i) caused by the 0.5 μM nifedipine. CONCLUSION:Ca(2+) channel blockers led to increased [Ca(2+)](i) in human skeletal muscle cells. The increase is thus scarcely affected by dantrolene treatment. Data provide a greater physiologic basis for avoiding the use of Ca(2+) channel blockers during MH crisis.
Authors: Gennady Cherednichenko; Alanna M Hurne; James D Fessenden; Eun Hui Lee; Paul D Allen; Kurt G Beam; Isaac N Pessah Journal: Proc Natl Acad Sci U S A Date: 2004-10-25 Impact factor: 11.205