Novel Expression of GABA(A) Receptors on Resistance Arteries That Modulate Myogenic Tone

摘要

The clinical administration of GABAergic medications leads to hypotension which has classically been attributed to the modulation of neuronal activity in the central and peripheral nervous systems. However, certain types of peripheral smooth muscle cells have been shown to express GABA(A) receptors, which modulate smooth muscle tone, by the activation of these chloride channels on smooth muscle cell plasma membranes. Limited prior studies demonstrate that non-human large-caliber capacitance blood vessels mounted on a wire myograph are responsive to GABA(A) ligands. We questioned whether GABA(A) receptors are expressed in human resistance arteries and whether they modulate myogenic tone. We demonstrate the novel expression of GABA(A) subunits on vascular smooth muscle from small-caliber human omental and mouse tail resistance arteries. We show that GABA(A) receptors modulate both plasma membrane potential and calcium responses in primary cultured cells from human resistance arteries. Lastly, we demonstrate functional physiologic modulation of myogenic tone via GABA(A) receptor activation in human and mouse arteries. Together, these studies demonstrate a previously unrecognized role for GABA(A) receptors in the modulation of myogenic tone in mouse and human resistance arteries.