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PMID: 10523413 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Protein kinase C regulation of K+ currents in rat ventricular myocytes and its modification by hormonal status.

The Journal of physiology ·Vol. 520 Pt 2 ·1999-10-15 ·Pages 439-49

Shimoni Y

Abstract

1. The effects of protein kinase C (PKC) activation on cardiac K+ currents were studied in rat ventricular myocytes, using whole-cell voltage clamp methods. Control rats were compared to hypothyroid or diabetic rats, in which PKC expression and activity were enhanced. 2. In control myocytes, two calcium-independent outward K+ currents, the transient It and the sustained Iss, were attenuated by 18.9 +/- 2.0 and 16.8 +/- 3.5 %, respectively (mean +/- s.e.m.), following addition of a synthetic analogue of diacylglycerol, DiC8 (20 microM). In myocytes from hypothyroid or diabetic rats, It and Iss were not affected by DiC8. 3. The effects of DiC8 were restored in myocytes from thyroidectomized rats by injection of physiological doses of tri-iodothyronine (T3; 10 microg kg-1 for 6-8 days). Incubating cells from diabetic rats with 100 nM insulin for 5-9 h also restored the ability of DiC8 to attenuate It and Iss. 4. The attenuation of K+ currents by DiC8 in control cells was absent in the presence of a peptide known to inhibit the translocation of the isoform PKCepsilon (EAVSKPLT, 24 microM introduced through the recording pipette). A scrambled peptide (LSETKPAV) was without effect. 5. Under hypothyroid conditions the inhibitory peptide restored the effects of DiC8 on It and Iss. These currents were attenuated by 11.9 +/- 1. 5 and 9.8 +/- 1.5 %, respectively, which was significantly (P < 0. 001) more than without the peptide or with the scrambled peptide. 6. These results show that the PKC-mediated suppression of cardiac K+ currents is normally mediated by PKCepsilon translocation. This effect is absent under hypothyroid and diabetic conditions, presumably due to prior PKC activation and translocation. A PKCepsilon translocation inhibitor restores the ability of DiC8 to attenuate K+ currents under hypothyroid conditions. This presumably reflects a (partial) reversal of a chronic translocation and a shift in the balance between PKC and its anchoring proteins.

MeSH Terms
Animals Cells, Cultured Diabetes Mellitus/metabolism Diglycerides/pharmacology Enzyme Activation Heart Ventricles Hypothyroidism/metabolism Insulin/pharmacology Isoenzymes/metabolism Male Myocardium/metabolism Patch-Clamp Techniques Potassium/metabolism Protein Kinase C/metabolism Protein Kinase C-epsilon Rats Rats, Sprague-Dawley Triiodothyronine/pharmacology
Chemicals
Diglycerides Insulin Isoenzymes Triiodothyronine 1,2-dioctanoylglycerol Prkce protein, rat Protein Kinase C Protein Kinase C-epsilon Potassium
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Shimoni Y
Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada. shimoni@ucalgary.ca
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Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
DOI
10.1111/j.1469-7793.1999.00439.x
Email
shimoni@ucalgary.ca
Published
1999-10-15
Pages
439-49
Language
English
Region
England
NLM ID
0266262
PMCID
PMC2269583
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1469-7793.1999.00439.x PMC Full Text View journal details
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