The Ionic Mechanism Of Securinine As The GABA_A Receptor Antagnist

L-Securinine(L-SEC),an alkaloid isolated from Securinega Suffructicosa,containing a fused indolizidine ring structure, is a GABA recognition site antagonist. The convulsant action of L-SEC is 'strychnine-like' and less potent than bicuculline. Our previous study demonstrated that intracerebroventricular administration of L-SEC removed the endogenous GABAergic tone in cardiovascular regulation and produced dose-dependent marked increase in arterial blood pressure, heart rate and the firing rate of the renal sympathetic nerve fibers. The ionic mechanisms by which the L-SEC as the GABA recognition site antagonist is not known. The present study was aimed to explore the ionic basis of L-SEC as GABA recognition site antagonist using whole cell patch clamp recordings in neurons freshly isolated from rat dorsal root ganglion (DRG).The results showed that:1. The majority of the cells examined (83/102, 81.37%) in the present experimentwere sensitive to external application of GABA (50-100 M) with an inward current. The inward current at a concentration of 100uM had apparent desensitization.2. The GABA activated current reversed at OmV, close to the estimated chloridereversal potential, and were blocked by bicuculline (100 M), this indicates thatthe inward current is due to activation of GAGAARs.3. The GAGA induced current was suppressed by (70.3 3.21)% when the DRGcells were pretreated with L-securinine (100 M) and 100 M bicucullinesuppressed the current by (86.26 5.62)%. 4. The muscimol was more effective at activating the inward current than theGABA. In 16 DRG cells, bicuculline (50 M) and L-SEC (50 M) blocked themuscimol induced current by (77.5 4.88)% and (51.42 6.25)% respectively. 5 The L-securinine partly blocks the voltage-activated barium current and maybeblock T-type calcium channel. 6. The L-securinine could not block or activate GABAB receptor.