Expression of cTnI-R145G affects shortening properties of adult rat cardiomyocytes.
The R145G amino acid exchange in the inhibitory subunit (cTnI) of cardiac troponin, which regulates muscle contraction, is related to familial hypertrophic cardiomyopathy. Information on its impact on contractility of adult cardiomyocytes is scarce. We studied shortening of adult rat cardiomyocytes before and during ss-adrenergic stimulation using adenovirus-driven expression of human cTnI-wild type (wt) and cTnI-R145G. Baseline sarcomere shortening was significantly decreased by cTnI-R145G expression. Upon ss-adrenergic stimulation using isoproterenol (ISO), nearly identical amplitudes of shortening were obtained with cells expressing cTnI-R145G and control cardiomyocytes (native and cTnI-wt). However, rates of shortening and relengthening were depressed in cTnI-R145G-expressing cells but were comparable to those of control cells upon addition of forskolin or ISO and ICI118,551. This indicates that cTnI-R145G expression influences the response to ss-adrenergic stimulation dependent on the receptor subtype.
Forschungslabor Molekulare Kardiologie, Bergmannsheil/St Josef-Hospital, Kliniken der Ruhr-Universität Bochum, Gudrunstr.56, 44791, Bochum, Germany.
Stephanie
S
Reis
Christoph
C
Littwitz
Sebastian
S
Preilowski
Andreas
A
Mügge
Ger J M
GJ
Stienen
Lutz
L
Pott
Kornelia
K
Jaquet
D000256:Adenoviridae / Q000235:genetics; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D002469:Cell Separation; D004558:Electric Stimulation; D005455:Fluorescent Antibody Technique; D005822:Genetic Vectors; D006352:Heart Ventricles; D006801:Humans; D007551:Isotonic Contraction / Q000502:physiology; D009154:Mutation / Q000502:physiology; D009200:Myocardial Contraction / Q000235:genetics / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011921:Rats, Inbred WKY; D019210:Troponin I / Q000235:genetics / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D019210:Troponin I