{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T23:06:40Z","timestamp":1778540800156,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2002,4,1]],"date-time":"2002-04-01T00:00:00Z","timestamp":1017619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2002,4]]},"abstract":"<jats:p>The effects of nitric oxide (NO) donors on the L\u2010type Ca<jats:sup>2+<\/jats:sup> current (<jats:italic>I<\/jats:italic><jats:sub>Ca,L<\/jats:sub>) and the muscarinic activated K<jats:sup>+<\/jats:sup> current (<jats:italic>I<\/jats:italic><jats:sub>K,ACh<\/jats:sub>) were studied in isolated rat cardiac myocytes. The nitrosothiol S\u2010nitroso\u2010<jats:italic>N<\/jats:italic>\u2010acetyl\u2010<jats:sc>d,d<\/jats:sc>\u2010penicillamine (SNAP, 1 p<jats:sc>m<\/jats:sc>\u20101 \u03bc<jats:sc>m<\/jats:sc>) strongly potentiated the stimulation of the <jats:italic>I<\/jats:italic><jats:sub>Ca,L<\/jats:sub> elicited by subthreshold concentrations of isoprenaline (Iso, 0.1\u20130.5 n<jats:sc>m<\/jats:sc>) in ventricular myocytes. The effect of SNAP was mimicked by 2\u2010(<jats:italic>N,N<\/jats:italic>\u2010diethylamino)\u2010diazenolate\u20102\u2010oxide (DEANO, 1 p<jats:sc>m<\/jats:sc>\u20101 n<jats:sc>m<\/jats:sc>), a NONOate that spontaneously releases NO in a pH\u2010controlled manner, and was blunted by 2\u2010(4\u2010carboxyphenyl)\u20104,4,5,5\u2010tetramethylimidazoline\u20101\u2010oxyl\u20103\u2010oxide (100 \u03bc<jats:sc>m<\/jats:sc>), a NO trap. 1H\u2010[1,2,4]Oxadiazolo[4,3\u2010a]quinoxaline\u20101\u2010one (10 \u03bc<jats:sc>m<\/jats:sc>), a guanylyl cyclase inhibitor, did not alter the effect of SNAP. SNAP (1 p<jats:sc>m<\/jats:sc>\u20101 \u03bc<jats:sc>m<\/jats:sc>) did not modify the effect of L858051 (0.1\u20130.3 \u03bc<jats:sc>m<\/jats:sc>), a forskolin analogue that activates adenylyl cyclase, on <jats:italic>I<\/jats:italic><jats:sub>Ca,L<\/jats:sub> and did not enhance the basal <jats:italic>I<\/jats:italic><jats:sub>Ca,L<\/jats:sub> in the presence of rolipram (1 \u03bc<jats:sc>m<\/jats:sc>), a phosphodiesterase type 4 inhibitor. Superfusion with Rp\u2010CPT\u2010cAMPS (500 \u03bc<jats:sc>m<\/jats:sc>), or internal dialysis with cAMP\u2010dependent protein kinase (cA\u2010PK) inhibitory peptide (PKI; 20 \u03bc<jats:sc>m<\/jats:sc>), inhibitors of the cA\u2010PK, blunted the effect of SNAP (1 n<jats:sc>m<\/jats:sc> and 1 \u03bc<jats:sc>m<\/jats:sc>) on the Iso\u2010stimulated (1\u2010100 p<jats:sc>m<\/jats:sc>) <jats:italic>I<\/jats:italic><jats:sub>Ca,L<\/jats:sub>. SNAP (1 n<jats:sc>m<\/jats:sc> and 1 \u03bc<jats:sc>m<\/jats:sc>) potentiated the threshold stimulation of <jats:italic>I<\/jats:italic><jats:sub>Ca,L<\/jats:sub> elicited by internal GTP\u2010\u03b3S (10 \u03bc<jats:sc>m<\/jats:sc>), a non\u2010hydrolysable analogue of GTP. SNAP (1 p<jats:sc>m<\/jats:sc>\u20101 \u03bc<jats:sc>m<\/jats:sc>) and DEANO (1 \u03bc<jats:sc>m<\/jats:sc>) potentiated the stimulation of <jats:italic>I<\/jats:italic><jats:sub>K,ACh<\/jats:sub> elicited by low concentrations of ACh (1\u20132 n<jats:sc>m<\/jats:sc>) in rat atrial myocytes. The threshold stimulation of <jats:italic>I<\/jats:italic><jats:sub>K,ACh<\/jats:sub> elicited by internal 5\u2032\u2010guanylylimidodiphosphate (10 \u03bc<jats:sc>m<\/jats:sc>) was also potentiated by NO donors. SNAP (1 \u03bc<jats:sc>m<\/jats:sc>) did not modify <jats:italic>I<\/jats:italic><jats:sub>K,ACh<\/jats:sub> reconstituted in human embryonic kidney 293 cells, in the absence or in the presence of ACh (1 or 10 n<jats:sc>m<\/jats:sc>). Taken together, these data suggest that NO is a cGMP\u2010independent modulator of G\u2010protein\u2010coupled muscarinic and \u03b2\u2010adrenergic receptor actions on cardiac ion channels. Although this action of NO seemed to occur at the level of G proteins, it appeared to require a component distinct from receptors, G proteins or their effectors.<\/jats:p>","DOI":"10.1113\/jphysiol.2001.012929","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:45:57Z","timestamp":1027773957000},"page":"411-424","source":"Crossref","is-referenced-by-count":24,"title":["NO donors potentiate the \u03b2\u2010adrenergic stimulation of <i>I<\/i><sub>Ca,L<\/sub> and the muscarinic activation of <i>I<\/i><sub>K,ACh<\/sub> in rat cardiac myocytes"],"prefix":"10.1113","volume":"540","author":[{"given":"Najah","family":"Abi\u2010Gerges","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabor","family":"Szabo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela S.","family":"Otero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodolphe","family":"Fischmeister","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre\u2010Fran\u00e7ois","family":"M\u00e9ry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,4]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.52.3.482"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.0117j.x"},{"key":"e_1_2_5_4_1","first-page":"628a","article-title":"Regulation of acetylcholine\u2010activated potassium current by nitric oxide in isolated rat atrial myocytes","volume":"80","author":"Abi\u2010Gerges N.","year":"2001","journal-title":"Biophysical Journal"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.37.26337"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00054a013"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0731-7085(98)00090-9"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.47.31186"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.108.4.277"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc4401.098515"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702607"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.11.5604"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.78.6.998"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1994.sp020132"},{"key":"e_1_2_5_15_1","first-page":"880","article-title":"Differences in effects of forskolin and an analog on calcium currents in cardiac myocytes suggest intracellular and extracellular sites of action","volume":"41","author":"Hartzell H. 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