Altered regulation of L‐type channels by protein kinase C and protein tyrosine kinases as a pathophysiologic effect in retinal degeneration1

Autor: Kirsten Steinhausen, Stefan Mergler, Michael Wiederholt, Olaf Strauss
Rok vydání: 1998
Předmět:
Zdroj: The FASEB Journal. 12:1125-1134
ISSN: 1530-6860
0892-6638
Popis: The effect of protein tyrosine kinases (PTK) on L-type calcium channels in cultured retinal pigmented epithelium (RPE) from rats with retinal dystrophy was investigated. Barium currents through Bay K 8644 (10−6 M) sensitive L-type channels were measured using the patch-clamp technique. The current density of L-type currents is twice as high and the inactivation time constants are much slower than in cells from nondystrophic control rats. Application of the PTK blockers genistein, lavendustin A, and herbimycin A (all 5×10−6 M) led to an increase of L-type currents. Intracellular application of pp60c-src (30 U/ml) via the patch pipette led to a transient decrease of L-type currents. The protein kinase A (PKA) and PKG blocker H9 (10−6 M) showed no effect on L-type currents. However, the protein kinase C blocker chelerythrine (10−5 M) reduced these currents. Up-regulation of PKC by 10−6 M 4β-phorbol-12 myristate-13 acetate (PMA) led to a decrease of L-type currents. Additional application of genistein led to ...
Databáze: OpenAIRE