Epidermal Growth Factor, Platelet-Derived Growth Factor AB, Insulin, Lysophosphatidic Acid, and Serum Modulate K+ Channel Properties in Chicken Embryo Fibroblasts

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Abstract
Serum-deprived chicken embryo fibroblasts (CEFs) were stimulated by newborn calf serum (NCS), epidermal growth factor (EGF), platelet-derived growth factor AB chain heterodimer (PDGF-AB), insulin, or lysophosphatidic acid (LPA), and their K+ current and K+ channel properties were investigated. After 12 h of serum deprivation, the K+ current amplitude of CEFs was 145 pA compared to 410 pA in control cells. Following mitogen application, the K+ current amplitude increased after 2 h by an amount that varied for the different mitogens. NCS, EGF, or LPA induced a delayed activating, Ca2+-dependent K+ (Kca) current that inactivated during prolonged depolarization, whereas PDGF-AB or insulin led to a fast activating KCa current that lacked inactivation. Stimulation by a combination of EGF plus PDGF-AB or EGF plus insulin affected the Kca current properties in a manner varying with the time of exposure. Single-channel analysis revealed that NCS, EGF, insulin, or LPA differentially modulated the number and the open-state probability of a KCa channel of 186 pS conductance (K186). In contrast, PDGF-AB strongly up-regulated the activity of a KCa channel of 65 pS conductance and in parallel down-regulated the activity of the K186 channel. Our results identify Kca channels as targets of receptor protein tyrosine kinase or LPA receptor signaling in CEFs and demonstrate a differential regulation of KCa channels by various mitogens.

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