Channel shutdown: a response of hippocampal neurons to adverse environments

Abstract

Stretch-activated ion channels have been discovered in the membrane of many types of cells, but their presence in neurons is uncertain. We used freshly dissociated rat hippocampal neurons to study the effect of hypotonic swelling but, surprisingly, the isolated neurons did not swell. Voltage-dependent whole-cell membrane currents mediated by K +, Na + and Ca 2+ were rapidly and reversibly suppressed during sudden exposure to strongly hypo-osmotic, hyper-osmotic or glucose deficient solutions. The amplitudes of the sustained components of K + and Ca 2+ currents were more depressed than transient currents, but the rate of decay of transient K + current greatly accelerated. The voltage dependence of activation and of steady state inactivation of residual K + and Ca 2+ currents were not shifted. The current holding membrane potential at −70 mV and therefore the conductance at that voltage were unchanged or somewhat decreased. Capacitive (charging) membrane current was not affected. Changes in tail current suggested moderate loss of cytosolic K + in some but not in all cells. We conclude that channel shutdown is a uniform response of neuron somata and proximal dendrites to various adverse environments. Hypothetically we propose that swelling was prevented in anisosmotic conditions because membrane water permeability decreased.