TGF-<f>β1</f> induces the expression of fast inactivating <f>K+</f> (<f>IA</f>) channels in rat vascular myofibroblasts

It is well established that transforming growth factor-<f>β1</f> (TGF-<f>β1</f>) can induce the transformation of fibroblasts to myofibroblasts. The molecular mechanisms of the phenotypic change remain unknown. The effect of TGF-<f>β1</f> on the expression of <f>K+</f> 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 <f>K+</f> current that can be electrophysiologically detected is non-inactivating. In myofibroblasts, induced by the treatment of fibroblasts with TGF-<f>β1</f>, we report the emergence of an additional transient outward <f>K+</f> current The TGF-<f>β1</f>-induced outward current is inhibited by 4-aminopyridine. <f>KV2.1</f>, 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 <f>IA</f> gene, <f>KV4.1</f>, can be detected only in myofibroblasts. The results suggest that TGF-<f>β1</f>-induced phenotypic transformation of vascular fibroblasts to myofibroblasts is accompanied by the induction of <f>IA</f> channels. [Copyright &y& Elsevier]