Altered transverse tubule dihydropyridine receptor binding in malignant hyperthermia

James M Ervasti, M. T. Claessens, James R Mickelson, C. F. Louis

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Transverse tubule (TT) membrane vesicles have been isolated from the skeletal muscle of normal and malignant hyperthermia-susceptible (MHS) pigs. MHS and normal TT did not differ in the distribution of the major proteins, cholesterol, or phospholipid content, (Na+ + K+)-ATPase activity, [3H]ouabain binding, Ca2+-ATPase activity, Mg2+-ATPase activity, or [3H]saxitoxin binding. Furthermore, in the presence of micromolar Ca2+, MHS and normal TT did not differ significantly in the K(D) values for either [3H]nitrendipine binding (2.7 ± 0.6 and 3.3 ± 0.5 nM, respectively) or (-)-[3H]desmethoxyverapamil ([3H]D888) binding (7.2 ± 0.9 and 6.4 ± 0.6 nM, respectively). However, in contrast to normal TT, MHS TT exhibited a significantly decreased B(max) for both [3H]nitrendipine binding (26.4 ± 5.4 for MHS versus 40.6 ± 3.7 pmol/mg protein for normal TT) and [3H]D888 binding (17.8 ± 7.0 for MHS versus 37.4 ± 5.9 pmol/mg protein for normal TT). At calcium concentrations greater than 0.1 mM, there was a greater inhibition of [3H]nitrendipine binding to normal than to MHS TT such that binding was now similar for both preparations. As with purified TT, [3H]nitrendipine binding to MHS muscle homogenates was significantly less than to normal muscle homogenates (109 ± 20 versus 211 ± 19 pmol/mg protein, for MHS and normal TT, respectively); this difference was not apparent when 100 mM CaCl2 was included in the binding medium. We conclude that the altered MHS TT dihydropyridine receptor properties may reflect an adaptation of the TT voltage sensing mechanism to the abnormal sarcoplasmic reticulum calcium release channel regulation in MHS muscle.

Original languageEnglish (US)
Pages (from-to)2711-2717
Number of pages7
JournalJournal of Biological Chemistry
Volume264
Issue number5
StatePublished - Jan 1 1989

Fingerprint

Nitrendipine
Malignant Hyperthermia
L-Type Calcium Channels
Muscle
Proteins
Saxitoxin
Calcium
Ca(2+) Mg(2+)-ATPase
Calcium-Transporting ATPases
Ouabain
Adenosine Triphosphatases
Phospholipids
Cholesterol
Muscles
Membranes
Electric potential
Sarcoplasmic Reticulum
Calcium Channels
Skeletal Muscle
4-desmethoxyverapamil

Cite this

Altered transverse tubule dihydropyridine receptor binding in malignant hyperthermia. / Ervasti, James M; Claessens, M. T.; Mickelson, James R; Louis, C. F.

In: Journal of Biological Chemistry, Vol. 264, No. 5, 01.01.1989, p. 2711-2717.

Research output: Contribution to journalArticle

@article{66c6a01301634f119f78572d729745f1,
title = "Altered transverse tubule dihydropyridine receptor binding in malignant hyperthermia",
abstract = "Transverse tubule (TT) membrane vesicles have been isolated from the skeletal muscle of normal and malignant hyperthermia-susceptible (MHS) pigs. MHS and normal TT did not differ in the distribution of the major proteins, cholesterol, or phospholipid content, (Na+ + K+)-ATPase activity, [3H]ouabain binding, Ca2+-ATPase activity, Mg2+-ATPase activity, or [3H]saxitoxin binding. Furthermore, in the presence of micromolar Ca2+, MHS and normal TT did not differ significantly in the K(D) values for either [3H]nitrendipine binding (2.7 ± 0.6 and 3.3 ± 0.5 nM, respectively) or (-)-[3H]desmethoxyverapamil ([3H]D888) binding (7.2 ± 0.9 and 6.4 ± 0.6 nM, respectively). However, in contrast to normal TT, MHS TT exhibited a significantly decreased B(max) for both [3H]nitrendipine binding (26.4 ± 5.4 for MHS versus 40.6 ± 3.7 pmol/mg protein for normal TT) and [3H]D888 binding (17.8 ± 7.0 for MHS versus 37.4 ± 5.9 pmol/mg protein for normal TT). At calcium concentrations greater than 0.1 mM, there was a greater inhibition of [3H]nitrendipine binding to normal than to MHS TT such that binding was now similar for both preparations. As with purified TT, [3H]nitrendipine binding to MHS muscle homogenates was significantly less than to normal muscle homogenates (109 ± 20 versus 211 ± 19 pmol/mg protein, for MHS and normal TT, respectively); this difference was not apparent when 100 mM CaCl2 was included in the binding medium. We conclude that the altered MHS TT dihydropyridine receptor properties may reflect an adaptation of the TT voltage sensing mechanism to the abnormal sarcoplasmic reticulum calcium release channel regulation in MHS muscle.",
author = "Ervasti, {James M} and Claessens, {M. T.} and Mickelson, {James R} and Louis, {C. F.}",
year = "1989",
month = "1",
day = "1",
language = "English (US)",
volume = "264",
pages = "2711--2717",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "5",

}

TY - JOUR

T1 - Altered transverse tubule dihydropyridine receptor binding in malignant hyperthermia

AU - Ervasti, James M

AU - Claessens, M. T.

AU - Mickelson, James R

AU - Louis, C. F.

PY - 1989/1/1

Y1 - 1989/1/1

N2 - Transverse tubule (TT) membrane vesicles have been isolated from the skeletal muscle of normal and malignant hyperthermia-susceptible (MHS) pigs. MHS and normal TT did not differ in the distribution of the major proteins, cholesterol, or phospholipid content, (Na+ + K+)-ATPase activity, [3H]ouabain binding, Ca2+-ATPase activity, Mg2+-ATPase activity, or [3H]saxitoxin binding. Furthermore, in the presence of micromolar Ca2+, MHS and normal TT did not differ significantly in the K(D) values for either [3H]nitrendipine binding (2.7 ± 0.6 and 3.3 ± 0.5 nM, respectively) or (-)-[3H]desmethoxyverapamil ([3H]D888) binding (7.2 ± 0.9 and 6.4 ± 0.6 nM, respectively). However, in contrast to normal TT, MHS TT exhibited a significantly decreased B(max) for both [3H]nitrendipine binding (26.4 ± 5.4 for MHS versus 40.6 ± 3.7 pmol/mg protein for normal TT) and [3H]D888 binding (17.8 ± 7.0 for MHS versus 37.4 ± 5.9 pmol/mg protein for normal TT). At calcium concentrations greater than 0.1 mM, there was a greater inhibition of [3H]nitrendipine binding to normal than to MHS TT such that binding was now similar for both preparations. As with purified TT, [3H]nitrendipine binding to MHS muscle homogenates was significantly less than to normal muscle homogenates (109 ± 20 versus 211 ± 19 pmol/mg protein, for MHS and normal TT, respectively); this difference was not apparent when 100 mM CaCl2 was included in the binding medium. We conclude that the altered MHS TT dihydropyridine receptor properties may reflect an adaptation of the TT voltage sensing mechanism to the abnormal sarcoplasmic reticulum calcium release channel regulation in MHS muscle.

AB - Transverse tubule (TT) membrane vesicles have been isolated from the skeletal muscle of normal and malignant hyperthermia-susceptible (MHS) pigs. MHS and normal TT did not differ in the distribution of the major proteins, cholesterol, or phospholipid content, (Na+ + K+)-ATPase activity, [3H]ouabain binding, Ca2+-ATPase activity, Mg2+-ATPase activity, or [3H]saxitoxin binding. Furthermore, in the presence of micromolar Ca2+, MHS and normal TT did not differ significantly in the K(D) values for either [3H]nitrendipine binding (2.7 ± 0.6 and 3.3 ± 0.5 nM, respectively) or (-)-[3H]desmethoxyverapamil ([3H]D888) binding (7.2 ± 0.9 and 6.4 ± 0.6 nM, respectively). However, in contrast to normal TT, MHS TT exhibited a significantly decreased B(max) for both [3H]nitrendipine binding (26.4 ± 5.4 for MHS versus 40.6 ± 3.7 pmol/mg protein for normal TT) and [3H]D888 binding (17.8 ± 7.0 for MHS versus 37.4 ± 5.9 pmol/mg protein for normal TT). At calcium concentrations greater than 0.1 mM, there was a greater inhibition of [3H]nitrendipine binding to normal than to MHS TT such that binding was now similar for both preparations. As with purified TT, [3H]nitrendipine binding to MHS muscle homogenates was significantly less than to normal muscle homogenates (109 ± 20 versus 211 ± 19 pmol/mg protein, for MHS and normal TT, respectively); this difference was not apparent when 100 mM CaCl2 was included in the binding medium. We conclude that the altered MHS TT dihydropyridine receptor properties may reflect an adaptation of the TT voltage sensing mechanism to the abnormal sarcoplasmic reticulum calcium release channel regulation in MHS muscle.

UR - http://www.scopus.com/inward/record.url?scp=0024537210&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024537210&partnerID=8YFLogxK

M3 - Article

C2 - 2536721

AN - SCOPUS:0024537210

VL - 264

SP - 2711

EP - 2717

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 5

ER -