Benzothiadiazides inhibit rapid glutamate receptor desensitization and enhance glutamatergic synaptic currents

摘要: A distinctive characteristic of the AMPA subset glutamate receptor channels is their remarkably rapid desensitization. family compounds, benzothiadiazides, described here that potently inhibit The structure- activity relationships these compounds are examined and actions cyclothiazide (CYZ), most potent in detail. At macroscopic level CYZ reduced desensitization, enhancing steady-state peak current produced by 1 mM quisqualate with EC50 values 14 12 microM, respectively, shifted concentration-response relation to left. slight outward rectification steady- state current-voltage relationship was CYZ. microscopic caused induce long bursts channel openings, greatly increased number repeated openings. 10 microM did not have measurable effects on fast component deactivation nor it statistically significant distribution faster components glutamate- induced burst duration. In contrast, amplitude significantly prolonged duration spontaneous miniature EPSCs. identification characterization this new gating modifiers may further facilitate investigation into mechanisms underlying desensitization physiological roles serve.