Bicuculline sensitive tonic current in RVLM neurons

Abstract

Neurons in the rostral ventrolateral medulla (RVLM) are best known for controlling arterial blood pressure and sympathetic outflow. It is well accepted that GABAergic inhibition in the RVLM is critical for the control of sympathetic outflow, and our previous study demonstrated that extrasynaptic GABAA receptors tonically inhibit RVLM neurons. In order to identify the subunit composition of GABAA receptors mediating the tonic current, we conducted whole‐cell patch‐clamp recordings from presympathetic RVLM neurons identified with retrograde viral labeling. First, we determined the effect of zolpidem on the amplitude of tonic current. Application of zolpidem (1μM), which activates GABAA receptors containing α1, α2 and/or α3 subunits, failed to modulate the amplitude of tonic current. Second, to determine the contribution of δ subunits containing GABAA receptors to the tonic current, we used THIP (4,5,6,7‐tetrahydroisoxazolo(5,4‐c)pyridin‐3‐ol), an agonist of δ subunits containing GABAA receptors. Application of THIP (10μM) produced no changes in the amplitude of tonic current in RVLM neurons. Then, a non‐selective voltage‐dependent K+‐channels blocker, 4‐aminopyridine (4‐AP), and a voltage‐dependent transient outward K+‐channels blocker, quinidine, was used. 4‐AP and quinidine induced a significant shift in the baseline current, corresponding to a 32.5±3.3pA and 78.5±8.5pA current, respectively. This data demonstrate that the tonic current sensitive to bicuculline methiodide in the RVLM is partially mediated by time‐ and voltage‐dependent transient outward K+‐channels, which may regulate the initial phase of repolarization modulating the voltage‐ and time‐dependence of action potentials in RVLM neurons.Support or Funding InformationThis work was supported by NIH HL122829 for AVD.