Related Experiment Video
Updated: Aug 27, 2026
Two Techniques to Create Hypoparathyroid Mice: Parathyroidectomy Using GFP Glands and Diphtheria-Toxin-Mediated Parathyroid Ablation
Published on: March 14, 2017
Slow calcium current is not reduced in malignant hyperthermic porcine myotubes
E M Gallant1, E M Balog, K G Beam
1Department of Veterinary PathoBiologoy, University of Minnesota, St. Paul, USA.
Abstract:
Malignant hyperthermia-susceptible (MHS) pigs express a sarcoplasmic reticulum (SR) Ca(2)+-release channel mutation that results in lower than normal contractile thresholds in skeletal muscles. In adult MHS pig muscles the L-type calcium current (ls) is also reduced. We tested the hypothesis that there is a causal relationship between ls and the lower contractile threshold by recording ls from MHS and normal porcine myotubes using the whole cell patch-clamp technique. Current voltage relationships for both MHS and normal myotubes were similar, with peak ls between +20 and +30 mV. Maximum ls amplitudes were not different from (normal: 4976 +/- 566 pA; MHS:6516 +/- 1088 pA) nor was ls specific density (normal: 9.0 +/- 0.8; MHS: 8.8 +/- 1.1 pA/pF). In both MHS and normal myotubes, both the dihydropyridine antagonist PN200-110 (200 nmol/L) and holding the membrane potential at -10mV for 5 min decreased ls significantly (by more than 50%). There was no apparent direct relationship between the mutation in the SR Ca(2)+ -release channel mutation on muscle development.
Insights
Malignant hyperthermia-susceptible pigs have a mutation affecting muscle contraction. This study found no direct link between the L-type calcium current and the lower contractile threshold in these pigs.
Area of Science:
- Physiology
- Molecular Biology
- Genetics
Background:
- Malignant hyperthermia-susceptible (MHS) pigs possess a mutation in the sarcoplasmic reticulum Ca(2)+-release channel.
- This mutation leads to reduced contractile thresholds in skeletal muscles.
- Adult MHS pigs also exhibit a diminished L-type calcium current (I(Ca,L)) in their muscles.
Purpose of the Study:
- To investigate a potential causal relationship between the L-type calcium current and the reduced contractile threshold in MHS pigs.
- To determine if alterations in I(Ca,L) contribute to the pathophysiology of malignant hyperthermia.
Main Methods:
- Whole-cell patch-clamp technique was employed to record I(Ca,L) from MHS and normal porcine myotubes.
- Current-voltage relationships were analyzed to assess I(Ca,L) characteristics.
- The effects of a dihydropyridine antagonist (PN200-110) and membrane potential changes on I(Ca,L) were examined.
Main Results:
- Current-voltage relationships and peak I(Ca,L) amplitudes were comparable between MHS and normal myotubes.
- Specific densities of I(Ca,L) were not significantly different between the two groups.
- Both the dihydropyridine antagonist and hyperpolarizing prepulse significantly reduced I(Ca,L) in both MHS and normal myotubes.
Conclusions:
- The study found no direct relationship between the sarcoplasmic reticulum Ca(2)+-release channel mutation and the L-type calcium current in MHS porcine myotubes.
- The mutation does not appear to directly impact muscle development through modulation of I(Ca,L).
- Further research is needed to elucidate the mechanisms underlying the reduced contractile threshold in MHS pigs.
