© 1995 American Heart Association, Inc.
Articles |
Inhibition of the Spontaneous Rate of Contraction of Neonatal Cardiac Myocytes by Protein Kinase C Isozymes
A Putative Role for the 
Isozyme
From the Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, Calif.
Correspondence to Daria Mochly-Rosen, Department of Molecular Pharmacology, Stanford University, School of Medicine, Stanford, CA 94305-5332.
Abstract Protein kinase C (PKC) enzymes regulate numerous
cardiac functions. In the present study, we determined the effects
of the PKC-activating drug 4-ß phorbol 12-myristate 13-acetate (4-ß
PMA) on the rate of contraction and correlated these changes with the
distribution and levels of 
-, ß-, 
-, 
-, and 
-PKC isozymes
by using neonatal rat cardiac myocytes in culture. Treatment with 0.3
to 100 nmol/L 4-ß PMA caused negative chronotropic effects on
contraction. This effect was maximal at a concentration of 3 nmol/L
4-ß PMA and correlated with redistribution of the - and -PKC
isozymes from the cytosolic to the particulate cell fraction. After a
1-hour treatment with 100 nmol/L PMA, the - and ß-PKC isozymes and
an 80-kD -like PKC isozyme were greatly diminished (downregulated),
yet the negative chronotropic effect was sustained. Therefore, our
results are most consistent with a role for the -PKC isozyme in
suppressing the contraction rate of neonatal rat cardiac myocytes.
Understanding the role(s) of individual PKC isozymes in the modulation
of cardiac functions may ultimately yield more selective targets for
therapies of cardiac disorders.
Key Words: phorbol ester • protein kinase C isozymes • cardiac myocytes • contraction • heart
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