Figure 5.

IGF-1 hyperpolarizes isolated SON neurons by inhibiting the mechanoreceptor current. A, Slow (23 mV/s) voltage ramps from -90 to -60 mV were applied onto a neuron under voltage clamp in control condition and in the presence of 50 ng/ml IGF-1. The currents from 24 successive ramps were averaged and fitted with linear regressions. The outward current induced by IGF-1 is associated with a decrease in the slope conductance, indicating the inhibition of a current active at rest. The reversal potential of this current (intersection of linear regression lines; arrow) was -36.0 mV. B, Application of Gd³⁺ induced a hyperpolarization of the neuron and completely and reversibly blocked the hyperpolarizing effect of IGF-1. Recording under current clamp is shown. C-E, Sensitivity of the hyperpolarizing effect of IGF-1 to the osmolarity of external medium. C, Application of a hyperosmotic medium (from 300 to 315 mOsm/L by adding 7.5 mm NaCl) induced a depolarization (activation of the mechanoreceptor current) and increased the amplitude of the hyperpolarization in response to IGF-1. Increased magnitude of the effect of IGF-1 effect is still present when the membrane potential is reset manually close to its original value (arrows). D, Application of a hypoosmotic medium (from 300 to 275 mOsm/L by removal of 12.5 mm NaCl) induced a hyperpolarization (inhibition of the mechanoreceptor current) and blocked the hyperpolarizing effect of IGF-1. E, Histogram summarizing the osmosensitivity of the effect of IGF-1.