Kito Yoshihiko, Suzuki Hikaru
Department of Physiology, Nagoya City University Medical School, Mizuho-ku, Nagoya 467-8601, Japan.
J Physiol. 2003 Jan 1;546(Pt 1):191-205. doi: 10.1113/jphysiol.2002.027607.
In the guinea pig gastric antrum, the effects of sodium nitroprusside (SNP), an NO donor, on pacemaker potentials were investigated in the presence of nifedipine. The pacemaker potentials consisted of primary and plateau components; SNP (> 1 microM) increased the frequency of occurrence of these pacemaker potentials, while inhibiting the plateau component. 1H-[1,2,4]-Oxadiazole [4,3-a] quinoxalin-1-one, an inhibitor of guanylate cyclase, had no effect on the excitatory actions of SNP on the frequency of pacemaker potentials. Other types of NO donor, (+/-)-S-nitroso-N-acetylpenicillamine, 3-morpholino-sydnonimine and 8-bromoguanosine 3'5'-cyclic monophosphate had no excitatory effect on pacemaker activity. Forskolin, an activator of adenylate cyclase, or 4,4'-diisothiocyano-stilbene-2,2'-disulphonic acid, an inhibitor of the Ca(2+)-activated Cl(-) channel, strongly attenuated the generation of pacemaker potentials, and SNP added in the presence of these chemicals restored the generation of pacemaker potentials. The pacemaker potentials evoked by SNP were abolished in low-Ca(2+) solution or by membrane depolarization with high-K(+) solution. The SNP-induced generation of pacemaker potentials was not prevented by cyclopiazonic acid, an inhibitor of internal Ca(2+)-ATPase, but was limited to a transient burst by iodoacetic acid, an inhibitor of glycolysis, carbonyl cyanide m-chlorophenyl-hydrazone, a mitochondrial protonophore, or 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester, an intracellular Ca(2+) chelator. These results suggest that the SNP-induced increase in the frequency of pacemaker potentials is related to the elevated intracellular Ca(2+) concentrations due to release from mitochondria, and these actions may be independent of the activation of guanylate cyclase.
在豚鼠胃窦中，在硝苯地平存在的情况下，研究了一氧化氮供体硝普钠（SNP）对起搏电位的影响。起搏电位由初级成分和平原成分组成；SNP（>1 microM）增加了这些起搏电位的发生频率，同时抑制了平原成分。鸟苷酸环化酶抑制剂1H-[1,2,4]-恶二唑[4,3-a]喹喔啉-1-酮对SNP对起搏电位频率的兴奋作用没有影响。其他类型的一氧化氮供体，（±）-S-亚硝基-N-乙酰青霉胺、3-吗啉代-西多胺和8-溴鸟苷3',5'-环一磷酸对起搏活动没有兴奋作用。腺苷酸环化酶激活剂福斯可林或钙激活氯通道抑制剂4,4'-二异硫氰酸芪-2,2'-二磺酸强烈减弱了起搏电位的产生，在这些化学物质存在的情况下添加SNP可恢复起搏电位的产生。在低钙溶液中或用高钾溶液进行膜去极化时，SNP诱发的起搏电位被消除。SNP诱导的起搏电位产生不受内质网钙ATP酶抑制剂环匹阿尼酸的阻止，但被糖酵解抑制剂碘乙酸、线粒体质子载体羰基氰化物间氯苯腙或细胞内钙螯合剂1,2-双（2-氨基苯氧基）乙烷-N,N,N',N'-四乙酸乙酰甲酯限制为短暂爆发。这些结果表明，SNP诱导的起搏电位频率增加与线粒体释放导致的细胞内钙浓度升高有关，并且这些作用可能与鸟苷酸环化酶的激活无关。
