An Electrophysiological Study on the Membrane Receptor-Mediated Action of Glucocorticoids in Mammalian Neurons

Abstract

The action of glucocorticoids (GC) on neuronal cell membrane was studied in isolated and superfused guinea pig coeliac ganglia by the intracellular recording technique. Cortisol succinate (F) hyperpolarized the membrane potential of 47 of 179 cells and changed the cell’s input resistance with a latency of less than 2 min in vitro. The effect persisted under low Ca²⁺/high Mg²⁺ superfusing condition and could be blocked by RU 38486, a competitive antagonist of GC cytosolic receptor. Cortisol-21-bovine albumin conjugant exhibited the same effect. Corticosterone (B) elicited hyperpolarization in another 15 of 83 cells, but dexamethasone (Dex) did not. Dex, however, depolarized 2 of 18 cells. Aldosterone, cholesterol and vehicle (ethyl alcohol) caused no detectable change in membrane potential. In vivo studies by iontophoretic application of steroids to hypothalamic paraventricular (PVN) neurons showed that F inhibited the unit discharges in 68 of 97 PVN neurons, and the effect could be antagonized by RU 38486. Dex excited 30 of 100 neurons. Estradiol (E) also inhibited the discharges, but this inhibition was not antagonized by RU 38486. The effect of GC on PVN neurons was also examined in hypothalamic slices including the paraventricular nucleus. B inhibited 28 of 104 units and excited 7 of 104 cells, and both effects could be antagonized by RU 38486. The threshold of inhibitory response was about 10^–7M, which is close to the physiological level of the hormone in plasma. The results suggest that GC can act non-genomically and specifically through its membrane receptor on the neuronal surface, and that there might be a chemical similarity between the membrane receptor and the traditional cytosolic GC receptor. It is also suggested that the modulatory action of GV might have some important physiological significance.

Rapid Neurophysiological Effects of Corticosterone on Medullary Neurons: Relationship to Stress-Induced Suppression of Courtship Clasping in an Amphibian

“…Release of CORT due to brief confinement stress or injection of as little as 2.5 nmol of CORT, results in a blockade of courtship clas ping that has a rapid onset (within 8 min) after intraperitoneal hormone administration [1,2], Recent investiga tion of the molecular basis for this behavioral effect of CORT has revealed the presence of a high affinity recep tor for CORT in neuronal membranes isolated from newt brain [2]. The characteristics of CORT binding to this re ceptor correspond well with the dose-effect, time course, subcellular localization, and pharmacological specificity of CORT action on newt sexual behavior, suggesting that CORT is acting on receptors in neuronal membranes rather than on classic intracellular glucocorticoid recep tors to effect its influence on clasping [2], There have been numerous previous investigations of neurophysiological actions of glucocorticoids, many of which have documented rapid, apparently nongenomic actions of these steroids [3][4][5][6][7][8][9], These prior electrophysiological studies, however, were not designed to analyze specific neurobehavioral actions of these steroids. The present study was conducted to assess CORT effects on aspects of newt brain function that could underlie the hormone's effect on clasping.…”

“…In the work with cat motor neurons, however, much higher doses of the gluco corticoid (30 mg/kg) were utilized, yet the effects were not as pronounced, in certain respects, as the more physiologi cal dosages employed in the present study. The increase in antidromic threshold and increase in refractory period for generation of the antidromic spike in newt reticulospinal neurons suggest a change in axonal excitability that could have resulted from a membrane hyperpolarization, as de scribed by Hall [33] or Chen et al [4].…”

Bidirectional Modulation of Hippocampal Long-Term Potentiation under Stress and No-Stress Conditions in Basolateral Amygdala-Lesioned and Intact Rats

“…The nature of this heterosynaptic input remains to be investigated. Because of the finding that rapid nongenomic effects of MR activation on neuronal membrane properties (Chen et al, 1991;Joels and de Kloet, 1994) can modulate locomotor activity novelty dependently (Sandi et al, 1996), probably by interaction with different neurotransmitter receptors (Majewska et al, 1986;McEwen et al, 1990;Schumacher, 1990), a rapid nongenomic effect of MR may also play a role in LTP modulation.…”

Unraveling the Time Domains of Corticosteroid Hormone Influences on Brain Activity: Rapid, Slow, and Chronic Modes

“…For instance, a pioneering study by Pfaff et al (1971) showed that peripherally administered corticosterone suppresses hippocampal firing within 20 min. Almost instantaneous though prolonged effects of corticosteroids were observed in PVN neurons antidromically identified through their projections to the median eminence (Saphier and Feldman, 1988;Chen et al, 1991); of these cells, nearly three quarters were inhibited by iontophoretically applied corticosterone or hydrocortisone.…”