VOLTAGE-GATED SODIUM-CHANNELS EXPRESSED IN THE HUMAN CEREBELLAR MEDULLOBLASTOMA CELL-LINE TE671

A characterization of the properties of voltage-gated sodium channels expressed in the human cerebellar medulloblastoma cell line TE671 is presented. Membrane currents were recorded under voltage clamp conditions using the patch clamp technique in both the whole-cell and the excised-patch configurations. Macroscopic sodium currents display a typical transient time course with a sigmoidal rise to a peak followed by an exponential decay. The rates of early activation and subsequent inactivation accelerate and approach a maximum in response to test potentials, V, of greater depolarization. The magnitude of peak sodium current increased from negligible values below V = -50 mV and reached a maximum at V = -3.6 mV ± 2.7 mV (mean ± S.E.M., n = 12). Sodium currents reversed at V = + 70 mV, near the predicted Nernst equilibrium potential for a Na+ selective channel. The peak sodium conductance, gpeak increased with depolarizing voltages to a maximum at V = ∼ 0 mV, exhibiting half-activation voltage at V {succeeds or equal to} -36.8 mV and an e-fold change in gpeak/9.5 mV. The Hodgkin-Huxley inactivation parameter h∞ indicates that at V = -73.6 mV half of the sodium currents were inactivated. Single channel current recordings demonstrated the occurrence of discrete events: the latency for first opening was shorter as the depolarizing pulse became more positive. The single-channel current amplitude was ohmic with a slope conductance, γ = 17.13 pS ± 0.66 pS. Sodium channel currents were reversibly blocked by tetrodotoxin (TTX). Thus, the TE671 human neurons in culture express a sodium channel which exhibits the voltage-gating properties, cation selectivity and neurotoxin sensitivity characteristic of 'classical' sodium channels of excitable cells. © 1990.