Four groups of mycoplasma-free commercial broilers were challenged with the R strain of Mycoplasma gallisepticum (MG) at 14 days of age. Groups received feed containing either no medication, or 500 ppm or 1000 ppm oxytetracycline (OTC) beginning at age 13 days, or 1000 ppm OTC beginning at age 15 days. All broilers were vaccinated with a live mild Massachusetts infectious bronchitis vaccine at 17 days of age. Air sac lesions were scored at age 24 days. In two almost identical experiments, all OTC treatment groups had significantly lower mean air sac lesion scores than the unmedicated challenged controls. Groups that were fed 1000 ppm OTC in feed had significantly lower mean air sac lesion scores than groups that were fed 500 ppm OTC in feed. There was no significant difference in mean air sac lesion scores between the groups fed 1000 ppm OTC in feed beginning at 13 days of age and those fed 1000 ppm OTC in feed beginning at 15 days of age.
Voltage-gated potassium (Kv) channels sense voltage and facilitate transmembrane flow of K+ to control the electrical excitability of cells. The Kv2.1 channel subtype is abundant in most brain neurons and its conductance is critical for homeostatic regulation of neuronal excitability. Many forms of regulation modulate Kv2.1 conductance, yet the biophysical mechanisms through which the conductance is modulated are unknown. Here, we investigate the mechanism by which the neuronal adhesion protein AMIGO1 modulates Kv2.1 channels. With voltage clamp recordings and spectroscopy of heterologously expressed Kv2.1 and AMIGO1 in mammalian cell lines, we show that AMIGO1 modulates Kv2.1 voltage sensor movement to change Kv2.1 conductance. AMIGO1 speeds early voltage sensor movements and shifts the gating charge-voltage relationship to more negative voltages. Fluorescence measurements from voltage sensor toxins bound to Kv2.1 indicate that the voltage sensors enter their earliest resting conformation, yet this conformation is less stable upon voltage stimulation. We conclude that AMIGO1 modulates the Kv2.1 conductance activation pathway by destabilizing the earliest resting state of the voltage sensors.
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