SLOW CALCIUM CURRENT IS NOT REDUCED IN MALIGNANT HYPERTHERMIC PORCINEMYOTUBES

Malignant hyperthermia-susceptible (MHS) pigs express a sarcoplasmic r eticulum (SR) Ca2+-release channel mutation that results in lower than normal contractile thresholds in skeletal muscles. In adult MHS pig m uscles the L-type calcium current (I-s) is also reduced. We tested the hypothesis that there is a causal relationship between I-s and the lo wer contractile threshold by recording I-s 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 I-s between +20 and +30 mV. Maximum I-s amplitudes were not different (normal: 4976 +/- 566 pA; MHS: 6516 +/- 1088 pA) nor was I-s specific density (normal: 9.0 +/- 0.8; MHS: 8.8 +/- 1.1 pA/pF). In both MHS an d normal myotubes, both the dihydropyridine antagonist PN200-110 (200 nmol/L) and holding the membrane potential at -10 mV for 5 min decreas ed I-s significantly (by more than 50%). There was no apparent direct relationship between the mutation in the SR Ca2+-release channel and l owered I-s. We concluded that reduced I-s in adult MHS pig muscles may be a secondary effect of the SR Ca2+-release channel mutation on musc le development. (C) 1996 John Wiley & Sons, Inc.