1. Epidermal growth factor increases if in rabbit SA node cells by activating a tyrosine kinase
- Author
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Hangang Yu, Ira S. Cohen, and Jiying Wu
- Subjects
medicine.medical_specialty ,Patch-Clamp Techniques ,medicine.drug_class ,Biophysics ,Tropomyosin receptor kinase B ,In Vitro Techniques ,Biochemistry ,Tropomyosin receptor kinase C ,Ion Channels ,Receptor tyrosine kinase ,Tyrosine-kinase inhibitor ,Membrane Potentials ,03 medical and health sciences ,0302 clinical medicine ,Heart Rate ,Epidermal growth factor ,Internal medicine ,medicine ,Animals ,Enzyme Inhibitors ,Tyrosine kinase ,Sinoatrial Node ,030304 developmental biology ,0303 health sciences ,if ,biology ,Kinase ,Cell Biology ,Protein-Tyrosine Kinases ,Genistein ,Enzyme Activation ,Endocrinology ,biology.protein ,Rabbits ,hormones, hormone substitutes, and hormone antagonists ,030217 neurology & neurosurgery ,Platelet-derived growth factor receptor - Abstract
Our previous results have demonstrated that tyrosine kinase inhibition reduces i(f) in rabbit SA node myocytes, suggesting that tyrosine kinases regulate i(f). One receptor tyrosine kinase the EGF receptor kinase is known to increase heart rate. To determine if this action is mediated through changes in i(f), we examined the effect of epidermal growth factor (EGF) on i(f) with the permeabilized patch-clamp technique. 0.1 microM EGF increased i(f) amplitude in response to single-step hyperpolarizations in the diastolic range of potentials. This increase was 20+/-3%, n=11 at -75 mV. This effect is caused by activating a tyrosine kinase because 50 microM genistein, a tyrosine kinase inhibitor, eliminated this EGF action. A two-step pulse protocol showed that maximal i(f) conductance was increased by EGF. We further examined this conductance change by constructing the activation curve. The maximal i(f) conductance was increased by 23% with no change in midpoint, V(1/2), control=-74+/-2 mV, V(1/2) EGF=-74+/-1 mV. Thus EGF acts via a tyrosine kinase to increase maximal i(f) conductance with no change in the voltage dependence of activation. These results suggest that EGF effects on i(f) contribute to the positive chronotropic effect of EGF on SA node.
- Published
- 2000