Regulation of Autonomic Motility in Human Gastric Muscle and the Gastroepiploic Artery by Stretch and pH

Human gastric motility is regulated by both slow wave activity and membrane excitability. Regulation of gastric function involves adapting motility through repetitive stretches during feeding and digestion. Alongside gastric motility, gastric vascular motility must also be accurately regulated. The physiological function of stretch-activated K⁺ channels has been demonstrated in the relaxation mechanisms of the uterus and bladder. For these reasons, this study was designed to investigate whether stretch-activated K⁺ channels are involved in the functional regulation of human gastric muscle and vessels. We examined human gastric body tissues and gastroepiploic arteries from patients who underwent gastrectomy using a conventional contractile measurement system and Western immunoblot. High concentrations of K⁺ (50 mM) induced tonic contraction (4 g) in human gastric circular muscle from the body. Acetylcholine (ACh, 10 µM) also induced an initial peak (3 g), tonic (1.1 g), and phasic contractions (1.5 g; 2.5 cycles/min). L-methionine, known to block TWIK (two-pore domain weak inward rectifying K_2P channel)-related K⁺ channels (TREK-1), produced sustained contraction (2 g) in gastric smooth muscle in the presence of a cocktail of K⁺ channel blockers. Additionally, channel inhibitors such as extracellular acidosis (MES ([pH]_o = 6.4)), quinidine, bupivacaine, and lidocaine enhanced spontaneous contractions by 224%, 183%, 138%, and 127% of control, respectively, in the presence of L-methionine. Concurrently, we analyzed the physiological role of TREK-1 and TASK-2 in the human gastroepiploic artery. The ring of the human gastroepiploic artery produced tonic contraction (2.8 g) under high K⁺ (50 mM). Following stimulation with high K⁺, the artery exhibited spontaneous vasoconstriction known as vasomotion (2.7 g; 0.13 cycles/min), which was completely inhibited by nifedipine, a voltage-dependent L-type Ca²⁺ channel (VDCC_L) blocker. BayK 8644, an activator of VDCC_L, induced vasomotion, which was also inhibited by nifedipine. In the human artery, L-methionine induced a vascular tonic contraction (0.15 g) and enhanced vasomotion by 179%. Additionally, lidocaine induced peak and tonic contractions of 1 g and 0.7 g, respectively. Both L-methionine and lidocaine also enhanced vasomotion induced by BayK 8644. The molecular presence of TREK-1 and TASK-2 was confirmed via Western blot in human gastric muscle, gastric mucosa, and artery, respectively. These findings suggest that TREK-1 and TASK-2 may be significant regulators of human gastric muscle and vascular motility.