Inhibition of inward rectifying potassium channels by activation of NMDA receptors on retinal horizontal cell / 中国药理学通报

Aim To study modulation of NMDA recep-tors on inward rectifying potassium channels through investigation of retinal horizontal cells. Methods Whole cell recording was conducted on isolated retinal horizontal cells for observation of inward-rectifying po-tassium currents before and after application of NMDA. Modulation of inward-rectifying currents by NMDA re-ceptor was also tested under calcium-free and chelation of intracellular calcium condition. Results Reduction of inward rectifying potassium currents was induced by activation of NMDA receptors. The effect was attenua-ted when calcium was removed. Conclusion Inhibi-tion of inward rectifying potassium channels can be in-duced by activation of NMDA receptors via intracellular calcium signals.

Aminopyridine-induced contracture in frog ventricle is due to calcium released from intracellular stores.

The aim of the study is to demonstrate the presence of intracellular calcium store in frog ventricle based on contractures induced by 4-aminopyridine in calcium-free media. Frog-ventricular strips were subjected to field stimulation at 0.2 Hz and the force of contraction was recorded after stabilization. The preparation was then kept quiescent for some time in solutions with different sodium concentrations, containing 0 or 1 mmol/L calcium. Caffeine, 4-aminopyridine (4-AP), or tetraethylammonium chloride was then added. Frog skeletal muscle preparations were used as positive controls for the caffeine experiments. Frog ventricular preparations did not develop contractures (sustained contractions) in the presence of caffeine (25 mmol/L), while frog skeletal muscle preparations developed caffeine-induced contractures. However, 4-AP (16 mmol/L) was able to induce contractures in quiescent frog ventricular preparations, even when they were superfused with calcium-free solution. 4-AP contractures in frog ventricle were seen in the presence of nifedipine also. Amplitude of 4-AP evoked contractures in frog ventricle were much larger in low sodium (30 mmol/L) and sodium-free (sodium substituted by lithium) solutions than in normal sodium solution, suggesting that the route of extrusion of the cytosolic calcium (released from intracellular stores by 4-AP) is the sodium calcium exchanger, which gets reversed in low sodium solutions. Tetraethylammonium chloride (TEA) was not able to induce contractures in frog ventricle suggesting that the contracture evoked by 4-AP is not due to its potassium channel blocking effect. In quiescent frog skeletal muscle preparations, caffeine as well as 4-AP induced contractures in calcium-free solutions. We therefore conclude that there is a caffeine-insensitive, 4-AP sensitive intracellular calcium store in the frog ventricle.

Pharmacological effects and application of caffeine / 医学研究生学报

Caffeine is a major ingredient of daily beverages including coffee, tea, coca-cola, et al, as well as one of most widely used drugs in the world. Caffeine is the stimulant of central nervous system and has positive effect on cardiovascular system. Moreover, it is able to promote secretion of gastric acid and alleviate migraine. It also play the wide-ranging roles in the other systems of the body. So, making a thorough investigation on caffeine not only has clinical significances, but also give a beneficial guide to the health and life. This review aims at highlighting the pharmacological effects of caffeine and exploring the relationship between the body and caffeine.

Altered vascular calcium regulation in hypertension

The present study was aimed at investigating whether the vascular calcium regulation is altered in hypertension. Two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension were made in rats, and their thoracic aortae were taken 4 weeks later. The isometric contractile response and calcium uptake of the endothelium-denuded aortic preparations were determined. Caffeine (0.1-35 mmol/L) induced a greater contraction in 2K1C and DOCA-salt hypertension than in normotensive control. When the vascular calcium store was functionally-depleted by a repeated exposure to caffeine, it took longer to reload the store and to resume the initial contraction force in response to caffeine in both 2K1C and DOCA-salt hypertension. The vascular 45Ca uptake following the functional depletion of the cellular store was also greater in both models of hypertension than in control. Ryanodine, calcium channel activator of the sarcoplasmic reticulum, attenuated the restoration of caffeine-induced vascular contraction, which was not affected by either 2K1C or DOCA-salt hypertension. Nifedipine, an L-type Ca2+ channel blocker, attenuated the restoration of caffeine-induced contraction, which was not affected by DOCA-salt hypertension, but was more pronounced in 2K1C hypertension. Nifedipine also diminished the vascular 45Ca uptake, which was not affected by DOCA-salt hypertension, but was more pronounced in 2K1C hypertension. Ouabain, a Na+, K+/-ATPase inhibitor, increased the caffeine-induced contraction by a similar magnitude in control and 2K1C hypertension, which was, however, markedly attenuated in DOCA-salt hypertension. Ouabain enhanced the vascular 45Ca uptake, the degree of which was not affected by 2K1C hypertension, but was markedly attenuated in DOCA-salt hypertension compared with that in control. Cyclopiazonic acid, a selective inhibitor of Ca2+/-ATPase of the sarcoplasmic reticulum, attenuated the restoration of caffeine-induced contraction, which was not affected by 2K1C hypertension, but was more marked in DOCA-salt hypertension. These results suggest that the increased vascular calcium storage may be attributed to an enhanced calcium influx in 2K1C hypertension, and to an impaired Na+/-K+ pump activity of the, cell membrane and subsequently increased calcium pump activity of the cellular store in DOCA-salt hypertension.