tetrodotoxin and Medulloblastoma

The inactivation of the sodium channels in human medulloblastoma cells was investigated with the whole-cell recording technique. The potential dependence of inactivation ("inactivation curve") was determined by imposing a series of prepulses of varying amplitude on the membrane potential and measuring the maximum sodium current flowing after each prepulse at the test potential of -20 mV. The time dependence of inactivation was investigated by determining inactivation curves with prepulses of variable duration. A prolongation of the prepulse increased the degree of inactivation, even when the prepulse duration was much greater than the time constant for fast inactivation. This is explained by the existence of two additional states of "intermediate" inactivation of the sodium channel, the transition to which is slower than that to the state of fast inactivation and faster than that to the state of slow inactivation. The antiarrhythmic drug tocainide had no effect on fast inactivation, but a strong effect on intermediate inactivation. This explains the use dependence of this drug. The reaction model given by Chiu (1977) for the transitions from the open into the closed state of inactivation and vice versa is extended.

Topics: Cerebellar Neoplasms; Humans; Lidocaine; Medulloblastoma; Models, Biological; Sodium Channels; Tetrodotoxin; Tocainide; Tumor Cells, Cultured

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 = approximately 0 mV, exhibiting half-activation voltage at V approximately equal to -36.8 mV and an e-fold change in gpeak/9.5 mV. The Hodgkin-Huxley inactivation parameter h infinity 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, gamma = 17.13 pS +/- 0.66 pS. Sodium channel currents were reversibly blocked by tetrodotoxin (TTX).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Cells, Cultured; Cerebellar Neoplasms; Humans; Medulloblastoma; Membrane Potentials; Sodium Channels; Tetrodotoxin; Tumor Cells, Cultured

Cell lines of medulloblastoma, retinoblastoma, and neuroblastoma, three childhood tumors derived from neuroectoderm, have been compared with respect to their neuronal properties. Neuroblastoma, a neural crest derivative, has been shown to express specific neuronal enzymes and the action potential sodium ionophore. Cell lines of medulloblastoma and retinoblastoma also express neuronal specific enzymes and therefore are considered to be of neuroblastic origin.

Topics: Acetylcholinesterase; Cell Line; Choline O-Acetyltransferase; Humans; Lithium; Medulloblastoma; Neuroblastoma; Neurons; Retinoblastoma; Tetrodotoxin; Tyrosine 3-Monooxygenase; Veratridine