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.