Regulation of L-Type Ca2+ Channels by Nitric Oxide Signalling in Guinea Pig Ventricular Myocytes

Nitric oxide (NO) is constitutively generated by cardiac myocytes and has important roles in cardiac function, including modifying L-type Ca2+ currents (ICa,L). The precise nature of this modification remains elusive with NO reported to increase, reduce or have biphasic effects on ICa,L. Here I explored the effects of NO signalling on ICa,L in both active period and resting period myocytes recorded from guinea pig ventricular myocytes using the perforated whole-cell switched voltage-clamp technique to maintain intracellular signalling pathways. Both cGMP-dependent and S-nitrosylation pathways were investigated. Isoprenaline (100 nM) significantly increased peak ICa,L by about two fold. Subsequent application of NO, using the NO donor SNAP, significantly decreased this enhanced ICa,L but had little effect on basal ICa,L. In contrast to these results obtained from active period myocytes, NO did not inhibit isoprenaline enhanced ICa,L in resting period myocytes. In active period myocytes NO inhibition of isoprenaline enhanced ICa,L was maintained in the presence of ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one), a soluble guanylyl cyclase (sGC) inhibitor. Direct activation of sGC or peripheral guanylyl cyclase independently of NO by BAY 60-2770 or ANP respectively, however, gave results similar to those observed with NO; although in some cells, BAY 60-2770 did not reduce isoprenaline enhanced ICa,L. Thus direct activation of sGC mimics the effect of NO, yet inhibiting sGC did not abolish NO reduction of isoprenaline enhanced ICa,L. These results suggest that NO modulates ICa,L through more than one mechanism. To investigate the S-nitrosylation pathway, denitrosylation was inhibited using N6022, a blocker of S-nitrosoglutathione reductase, an enzyme involved in denitrosylation. This treatment, either completely abolished or slowed significantly the rate of development of isoprenaline enhancement of ICa,L in cells exposed previously to NO. In conclusion, NO inhibition of isoprenaline enhanced ICa,L involves at least two signalling pathways; a cGMP-dependent and the S-nitrosylation pathway in active period myocytes

Analysis of Some Heavy Metals and Organic Acids in Ficus carica Growing Adjacent in the Serpentine Soil in Sulaimani/Kurdistan, Iraq

Serpentine soil refers to soil having magnesium-rich minerals such as chrysotile, lizardite, and antigorite. Fig (Ficus carica) is a plant of major importance in the world. It is a nourishing food and is used in industrial productions. This study analyzes the distribution of heavy metal contents such as nickel, cobalt, zinc, and manganese in different parts of this plant, such as its leaves, stems, and fruits. Furthermore, the organic acid content, including citric acid, fumaric acid, malic acid, and oxalic acid, was estimated. The studied area is known as Kunjirin which is a village located in the northwestern extension of the Zagros-fold-thrust belt in Mawat town, northeast of Sulaimani Province, Kurdistan Region of Iraq. The results show that there are significant differences in heavy metal contents among the plant organs except for zinc. The lowest level of heavy metals is in the fruits, while the highest amount of the heavy metal content is in the leaves. Moreover, the organic acids were unequally distributed in the plant organs. However, the lowest level of organic acids are found in the stem, while the highest concentration of the organic acids are found in the fruit part of the plant. The present study concludes that the level of heavy metals in the fruit part is within the legally admitted limits. This indicates that it is normal for human beings and animals to consume such fruits