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Protein kinase C regulation of K + currents in rat ventricular myocytes and its modification by hormonal status
Author(s) -
Shimoni Y.
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.00439.x
Subject(s) - protein kinase c , endocrinology , medicine , myocyte , diacylglycerol kinase , microinjection , chemistry , kinase , biology , biochemistry
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 I t and the sustained I ss , 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 μ m ). In myocytes from hypothyroid or diabetic rats, I t and I ss 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 (T 3 ; 10 μg kg −1 for 6–8 days). Incubating cells from diabetic rats with 100 n m insulin for 5–9 h also restored the ability of DiC8 to attenuate I t and I ss . 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 PKCɛ (EAVSKPLT, 24 μ m , 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 I t and I ss . 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 PKC ɛ translocation. This effect is absent under hypothyroid and diabetic conditions, presumably due to prior PKC activation and translocation. A PKCɛ 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.