Functional differences of Na⁺/Ca²⁺exchanger expression in Ca²⁺transport system of smooth muscle of guinea pig stomach

Abstract

The plasma membrane ATP-dependent Ca2+ pump and the Na+/Ca2+ exchanger (NCX) are the major means of Ca2+ extrusion in smooth muscle. However, little is known regarding distribution and function of the NCX in guinea pig gastric smooth muscle. The expression pattern and distribution of NCX isoforms suggest a role as a regulator of Ca2+ transport in cells. Na+ pump inhibition and the consequent to removal of K+ caused gradual contraction in fundus. In contrast, the response was significantly less in antrum. Western blotting analysis revealed that NCX1 and NCX2 are the predominant NCX isoforms expressed in stomach, the former was expressed strongly in antrum, whereas the latter displayed greater expression in fundus. Isolated plasma membrane fractions derived from gastric fundus smooth muscle were also investigated to clarify the relationship between NCX protein expression and function. Na+-dependent Ca2+ uptake increased directly with Ca2+ concentration. Ca2+ uptake in Na+-loaded vesicles was markedly elevated in comparison with K+-loaded vesicles. Additionally, Ca2+ uptake by the Na+- or K+-loaded vesicles was substantially higher in the presence of A23187 than in its absence. The result can be explained based on the assumption that Na+ gradients facilitate downhill movement of Ca2+. Na+-dependent Ca2+ uptake was abolished by the monovalent cationic ionophore, monensin. NaCl enhanced Ca2+ efflux from vesicles, and this efflux was significantly inhibited by gramicidin. Results documented evidence that NCX2 isoform functionally contributes to Ca2+ extrusion and maintenance of contraction-relaxation cycle in gastric fundus smooth muscle.

Sodium-Calcium Exchange in Intracellular Calcium Handling of Human Airway Smooth Muscle

“…On the other hand, Schuster et al found that in rat mesenteric artery, norepinephrine induced [Ca 2+ ] i oscillations were largely unaffected by KBR7943 (in contrast to inhibition of L-type Ca 2+ channels) [54]. In other smooth muscles, NCX-mediated Ca 2+ efflux appears to be important for [Ca 2+ ] i homeostasis in guinea pig stomach [55]. In urethral interstitial cells of Cajal, NCX-mediated Ca 2+ influx is important for pacemaker activity [56].…”

Inhibitory mechanisms of docosahexaenoic acid on carbachol-, angiotensin II-, and bradykinin-induced contractions in guinea pig gastric fundus smooth muscle

“…The remaining contractile component may be dependent on extracellular Ca 2+ influx through SOCCs, which could not be completely suppressed by SKF-96365 (3 × 10 −5 M). Candidates other than SOCCs are LOE-908/SKF-96365-insensitive ROCCs and the reverse mode of the Na + /Ca 2+ exchanger 37 , 38 .…”

Roles of Na+/Ca2+exchanger 1 in digestive system physiology and pathophysiology

“…It is known that the plasma membrane Ca 2+ -ATPase (PMCA), NCX, and the endoplasmic reticulum (ER) Ca 2+ -ATPase are the main mechanisms for the transport of intracellular Ca 2+ to the extracellular space of gastric smooth muscle cells[42,43]. Studies have shown that NCX1 is widely expressed in the antrum of guinea pigs, while NCX2 has higher expression in the fundus[44]. Researchers believe that different NCX subtypes, which have different physiological functions, are expressed in different parts of the stomach and regulate each other.…”

“…Researchers believe that different NCX subtypes, which have different physiological functions, are expressed in different parts of the stomach and regulate each other. NCX1 is mainly involved in gastric antral motility, while NCX2 mainly changes the intracellular Ca 2+ homeostasis in fundus smooth muscle cells to control the contraction and relaxation of the fundus smooth muscle[44]. This information suggests that the NCX family may control the movement of the whole stomach by controlling the movement of the gastric antrum and fundus smooth muscle.…”