TGF-beta1 induces the expression of fast inactivating K+ (I(A)) channels in rat vascular myofibroblasts.
It is well established that transforming growth factor-beta1 (TGF-beta1) can induce the transformation of fibroblasts to myofibroblasts. The molecular mechanisms of the phenotypic change remain unknown. The effect of TGF-beta1 on the expression of K(+) channels in cultured rat vascular fibroblasts was investigated by using the patch-clamp technique and quantitative RT-PCR. In fibroblasts, the only voltage-dependent outward K(+) current that can be electrophysiologically detected is non-inactivating. In myofibroblasts, induced by the treatment of fibroblasts with TGF-beta1, we report the emergence of an additional transient outward K(+) current The TGF-beta1-induced outward current is inhibited by 4-aminopyridine. K(V2.1), the transcript for a non-inactivating potassium channel gene, was detected by quantitative RT-PCT in both cultured fibroblasts and myofibroblasts. In contrast, the transcript of the transient I(A) gene, K(V4.1), can be detected only in myofibroblasts. The results suggest that TGF-beta1-induced phenotypic transformation of vascular fibroblasts to myofibroblasts is accompanied by the induction of I(A) channels.
Wu
Ming-ming
MM
Department of Physiology and Biophysics, Research Center of Brain Science, School of Life Sciences, Fudan University, Shanghai 200433, China.
Gao
Ping-jin
PJ
Jiao
Song
S
Zhu
Ding-liang
DL
Zang
Zhi-hong
ZH
Mei
Yan-ai
YA
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002478:Cells, Cultured; D018999:Charybdotoxin / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D026902:Potassium Channel Blockers; D015221:Potassium Channels; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D018999:Charybdotoxin; D015761:4-Aminopyridine