engleski

Effects of central application of GABAc receptor antagonist on phrenic nerve activity

Introduction: Synaptic inhibition mediated by γ -amino butyric acid (GABA) has important role in the generation and control of basic respiratory rhythm. Two major types of ionotropic receptors of GABA receptors have been identified, termed GABAA and GABAC receptors. The GABAA and GABAC receptors are chloride channels that mediate fast synaptic inhibition and are selectively blocked by the alkaloid bicuculline and (1, 2, 5, 6-tetrahydropyridin-4-yl)methylophosphinic acid TPMPA, respectively. No previous studies are available on the possible role mediated by novel subtype of ionotropic GABAC receptors in the breathing control of adult rat. The main objective of this study was to demonstrate whether central microinjections of selective antagonist of GABAC receptors TPMPA, in the different regions of the ventral respiratory group, have influence on respiration, as shown in the phrenic nerve activity. Materials and methods: Experiments were performed on urethane anaesthetized, spontaneously breathing, billateraly vagotomized adult male Sprague-Dawley rats weighing 300-330 g. Femoral artery was cannulated for blood pressure monitoring. The phrenic nerve recordings monitored central respiratory activity. Phrenic nerve was dissected using dorsal approach at the level of C5 nerve rootlet, mounted on bipolar silver wire electrodes. The rats were placed in a prone position in a stereotaxic instrument. Occipital craniotomy exposed the dorsal surface of the brainstem. That approach provided clear access to the obex that was used as referral point for measurements through the region of VRG. The single barrel micropipettes were filled with artificial cerebrospinal fluid (aCSF) or TPMPA (300 μ M) and used for unilateral drug delivery. Results: Unilateral microinjection of TPMPA into the VRG produced decrease of peak amplitude of phrenic nerve discharge when microinjected at the most caudal parts of the VRG. Microinjections of TPMPA in more rostral parts of the VRG elicited no change in the rhythm or pattern of phrenic nerve activity. Conclusion: These data suggest possible involvement of GABAC receptors, a specific subtype of ionotropic GABA receptors in the breathing control in rats.

Phrenic nerve recordings; GABA

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