[3H]-nitrendipine binding sites in normal and cardiomyopathic hamsters: Absence of a selective increase in putative calcium channels in cardiomyopathic hearts

Susan E. Howlett; Victor F. Rafuse; Tessa Gordon

doi:10.1093/cvr/22.11.840

[³H]-nitrendipine binding sites in normal and cardiomyopathic hamsters: Absence of a selective increase in putative calcium channels in cardiomyopathic hearts

Susan E. Howlett, Victor F. Rafuse, Tessa Gordon

Résultat de recherche: Review article › examen par les pairs

15 Citations (Scopus)

Résumé

The number of putative calcium channels in cardiac muscle from young adult hamsters (60 days old) was compared in normal (F₁B) hamsters and two different mutant strains (CHF 146 and Bio 14.6) which express cardiomyopathy and muscular dystrophy. Equilibrium binding assays of high affinity sites for [³H]-nitrendipine in ventricular homogenate preparations showed that the maximum number of [³H]-nitrendipine binding sites (B_max), which corresponds to the number of putative calcium channels, was not significantly different in normal and cardiomyopathic hearts: 79(SEM9), 64(14) and 69(10) fmol·mg^-1 protein in 4-6 hearts from F₁B, Bio 14.6 and CHF 146 hamster strains, respectively. Similar results were obtained with binding data after partial purification of the preparation. These data are in agreement with earlier studies comparing two normal strains (CHF 148 and random bred Syrian hamsters) with cardiomyopathic (CHF 146) hamsters, and conflict with other studies comparing normal and cardiomyopathic hamsters. Comparisons with the conflicting data suggest (a) that change in the number of high affinity [³H]-nitrendipine binding sites is not responsible for calcium overload and cell necrosis in cardiomyopathy, and (b) that increased numbers of low affinity [³H]-nitrendipine binding sites may emerge in cardiomyopathic hearts.

Langue d'origine	English
Pages (de-à)	840-846
Nombre de pages	7
Journal	Cardiovascular Research
Volume	22
Numéro de publication	11
DOI	https://doi.org/10.1093/cvr/22.11.840
Statut de publication	Published - nov. 1988
Publié à l'externe	Oui

Note bibliographique

Funding Information:
Widely divergent estimates of KD suggest a more interesting explanation. High and low affinity [3H]-NTP binding sites, which differ by two or three orders of magnitude, can be demonstrated usin an appropriate range of ['HI-NTP concentration^.'^ 25 The KD for the high affiiity site in cardiac muscle is 0.1-0.2 nmol.litre-' lo Is 17-22 when concentrations of [3H]-NTP from ten fold less than the KD to five or ten fold greater (as described inI6) are selected as illustrated in the example in fig 4a. The KD values for the high affinity site obtained by Wagner et up using a concentration range of about 0.1 to 3 or 5 nmol.litre-' were 0.46 to 0.60 nmol-litre-', which is five or six times greater than typically reported. This range of [3H]-NTP concentrations is midway between appropriate free concentrations for sampling high and low affinity binding sites as illustrated by the filled squares in fig 4b. The line is drawn through these points to illustrate how the Scatchard data of previous workers were obtained. In fact, this line is the transition between high and low affinity binding sites This project was supported by the Alberta Heart Foundation. Susan Howlett i:; an Alberta Heritage Foundation for Medical Xesearch (AHFMR) postdoctoral fellow and Tessa Gordon is an AHFMR scholar. The authors wish to thank Dr M Michalak and Dr WF Dryden for reading an earlier draft of this manuscript.

ASJC Scopus Subject Areas

Physiology
Cardiology and Cardiovascular Medicine
Physiology (medical)

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10.1093/cvr/22.11.840

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title = "[3H]-nitrendipine binding sites in normal and cardiomyopathic hamsters: Absence of a selective increase in putative calcium channels in cardiomyopathic hearts",

abstract = "The number of putative calcium channels in cardiac muscle from young adult hamsters (60 days old) was compared in normal (F1B) hamsters and two different mutant strains (CHF 146 and Bio 14.6) which express cardiomyopathy and muscular dystrophy. Equilibrium binding assays of high affinity sites for [3H]-nitrendipine in ventricular homogenate preparations showed that the maximum number of [3H]-nitrendipine binding sites (Bmax), which corresponds to the number of putative calcium channels, was not significantly different in normal and cardiomyopathic hearts: 79(SEM9), 64(14) and 69(10) fmol·mg-1 protein in 4-6 hearts from F1B, Bio 14.6 and CHF 146 hamster strains, respectively. Similar results were obtained with binding data after partial purification of the preparation. These data are in agreement with earlier studies comparing two normal strains (CHF 148 and random bred Syrian hamsters) with cardiomyopathic (CHF 146) hamsters, and conflict with other studies comparing normal and cardiomyopathic hamsters. Comparisons with the conflicting data suggest (a) that change in the number of high affinity [3H]-nitrendipine binding sites is not responsible for calcium overload and cell necrosis in cardiomyopathy, and (b) that increased numbers of low affinity [3H]-nitrendipine binding sites may emerge in cardiomyopathic hearts.",

author = "Howlett, {Susan E.} and Rafuse, {Victor F.} and Tessa Gordon",

note = "Funding Information: Widely divergent estimates of KD suggest a more interesting explanation. High and low affinity [3H]-NTP binding sites, which differ by two or three orders of magnitude, can be demonstrated usin an appropriate range of ['HI-NTP concentration^.'^ 25 The KD for the high affiiity site in cardiac muscle is 0.1-0.2 nmol.litre-' lo Is 17-22 when concentrations of [3H]-NTP from ten fold less than the KD to five or ten fold greater (as described inI6) are selected as illustrated in the example in fig 4a. The KD values for the high affinity site obtained by Wagner et up using a concentration range of about 0.1 to 3 or 5 nmol.litre-' were 0.46 to 0.60 nmol-litre-', which is five or six times greater than typically reported. This range of [3H]-NTP concentrations is midway between appropriate free concentrations for sampling high and low affinity binding sites as illustrated by the filled squares in fig 4b. The line is drawn through these points to illustrate how the Scatchard data of previous workers were obtained. In fact, this line is the transition between high and low affinity binding sites This project was supported by the Alberta Heart Foundation. Susan Howlett i:; an Alberta Heritage Foundation for Medical Xesearch (AHFMR) postdoctoral fellow and Tessa Gordon is an AHFMR scholar. The authors wish to thank Dr M Michalak and Dr WF Dryden for reading an earlier draft of this manuscript.",

year = "1988",

month = nov,

doi = "10.1093/cvr/22.11.840",

language = "English",

volume = "22",

pages = "840--846",

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T1 - [3H]-nitrendipine binding sites in normal and cardiomyopathic hamsters

T2 - Absence of a selective increase in putative calcium channels in cardiomyopathic hearts

AU - Howlett, Susan E.

AU - Rafuse, Victor F.

AU - Gordon, Tessa

N1 - Funding Information: Widely divergent estimates of KD suggest a more interesting explanation. High and low affinity [3H]-NTP binding sites, which differ by two or three orders of magnitude, can be demonstrated usin an appropriate range of ['HI-NTP concentration^.'^ 25 The KD for the high affiiity site in cardiac muscle is 0.1-0.2 nmol.litre-' lo Is 17-22 when concentrations of [3H]-NTP from ten fold less than the KD to five or ten fold greater (as described inI6) are selected as illustrated in the example in fig 4a. The KD values for the high affinity site obtained by Wagner et up using a concentration range of about 0.1 to 3 or 5 nmol.litre-' were 0.46 to 0.60 nmol-litre-', which is five or six times greater than typically reported. This range of [3H]-NTP concentrations is midway between appropriate free concentrations for sampling high and low affinity binding sites as illustrated by the filled squares in fig 4b. The line is drawn through these points to illustrate how the Scatchard data of previous workers were obtained. In fact, this line is the transition between high and low affinity binding sites This project was supported by the Alberta Heart Foundation. Susan Howlett i:; an Alberta Heritage Foundation for Medical Xesearch (AHFMR) postdoctoral fellow and Tessa Gordon is an AHFMR scholar. The authors wish to thank Dr M Michalak and Dr WF Dryden for reading an earlier draft of this manuscript.

PY - 1988/11

Y1 - 1988/11

N2 - The number of putative calcium channels in cardiac muscle from young adult hamsters (60 days old) was compared in normal (F1B) hamsters and two different mutant strains (CHF 146 and Bio 14.6) which express cardiomyopathy and muscular dystrophy. Equilibrium binding assays of high affinity sites for [3H]-nitrendipine in ventricular homogenate preparations showed that the maximum number of [3H]-nitrendipine binding sites (Bmax), which corresponds to the number of putative calcium channels, was not significantly different in normal and cardiomyopathic hearts: 79(SEM9), 64(14) and 69(10) fmol·mg-1 protein in 4-6 hearts from F1B, Bio 14.6 and CHF 146 hamster strains, respectively. Similar results were obtained with binding data after partial purification of the preparation. These data are in agreement with earlier studies comparing two normal strains (CHF 148 and random bred Syrian hamsters) with cardiomyopathic (CHF 146) hamsters, and conflict with other studies comparing normal and cardiomyopathic hamsters. Comparisons with the conflicting data suggest (a) that change in the number of high affinity [3H]-nitrendipine binding sites is not responsible for calcium overload and cell necrosis in cardiomyopathy, and (b) that increased numbers of low affinity [3H]-nitrendipine binding sites may emerge in cardiomyopathic hearts.

AB - The number of putative calcium channels in cardiac muscle from young adult hamsters (60 days old) was compared in normal (F1B) hamsters and two different mutant strains (CHF 146 and Bio 14.6) which express cardiomyopathy and muscular dystrophy. Equilibrium binding assays of high affinity sites for [3H]-nitrendipine in ventricular homogenate preparations showed that the maximum number of [3H]-nitrendipine binding sites (Bmax), which corresponds to the number of putative calcium channels, was not significantly different in normal and cardiomyopathic hearts: 79(SEM9), 64(14) and 69(10) fmol·mg-1 protein in 4-6 hearts from F1B, Bio 14.6 and CHF 146 hamster strains, respectively. Similar results were obtained with binding data after partial purification of the preparation. These data are in agreement with earlier studies comparing two normal strains (CHF 148 and random bred Syrian hamsters) with cardiomyopathic (CHF 146) hamsters, and conflict with other studies comparing normal and cardiomyopathic hamsters. Comparisons with the conflicting data suggest (a) that change in the number of high affinity [3H]-nitrendipine binding sites is not responsible for calcium overload and cell necrosis in cardiomyopathy, and (b) that increased numbers of low affinity [3H]-nitrendipine binding sites may emerge in cardiomyopathic hearts.

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