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Modulation of CFTR activity alters submaximal β‐adrenergic receptor stimulated cardiomyocyte contraction rate
Author(s) -
Sellers Zachary M,
Xiang Yang,
Best Philip M
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.953.10
Subject(s) - contraction (grammar) , endocrinology , medicine , stimulation , chemistry , ec50 , adrenergic , myocyte , receptor , adrenergic receptor , in vitro , biochemistry
Previously we found that CFTR regulates the contraction rate of spontaneously beating neonatal ventricular cardiomyocytes. In this study we examined if CFTR is involved in β‐adrenergic receptor (β‐AR) stimulated increases in contraction rate. Spontaneous beating cardiomyocytes were generated by isolation and culture of mouse neonatal ventricular myocytes. Isoproterenol dose‐dependently increased contraction rates with an EC50 of 16.6 nM. Inhibition or knockout of CFTR led to a loss of submaximal β‐AR stimulation, resulting in a right‐shift of the dose response curve with an EC50 of 66.7 nM and 31.2 nM, respectively. This targeted response to submaximal β‐AR stimulated contraction rates was specific to CFTR as inhibition of volume‐ or Ca 2+ ‐activated Cl − channels affected both submaximal and maximal concentrations. Furthermore, pre‐activation of CFTR with genistein or PG‐01 potentiated submaximal isoproterenol stimulated contraction rates, resulting in a left‐shift of the dose response curve with an EC50 of 1.1 nM and 0.6 nM, respectively. Our results indicate that CFTR plays a distinct role in regulating contraction rate responses to submaximal, but not maximal, β‐AR stimulation. Future work will be necessary to determine if individuals with alterations in CFTR activity (i.e. cystic fibrosis patients) may be at increased risk for cardiac abnormalities. Funded by the AHA, NIH, University of Illinois.