{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:42:33Z","timestamp":1773661353143,"version":"3.50.1"},"reference-count":6,"publisher":"S. Karger AG","issue":"5","license":[{"start":{"date-parts":[[1998,1,1]],"date-time":"1998-01-01T00:00:00Z","timestamp":883612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[1998,1,1]],"date-time":"1998-01-01T00:00:00Z","timestamp":883612800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Vasc Res"],"published-print":{"date-parts":[[1998]]},"abstract":"In the present study, we investigated the actions of calmodulin (CaM) and CaM-dependent protein kinase II (CaMK-II) on the L-type Ca<sup>2+<\/sup> currents (I<sub>Ca(L)<\/sub>) of cultured vascular smooth muscle (VSM) cells (A7r5 cell line), using the whole-cell voltage clamp method. The peak I<sub>Ba<\/sub> (Ca<sup>2+<\/sup> channel using 5 m<i>M<\/i> Ba<sup>2+<\/sup> as charge carrier) was evoked every 15 s by a test potential to +10 mV from a holding potential of \u201360 mV. To test the effect of CaM on I<sub>Ba<\/sub>, 1 \u00b5<i>M<\/i> calmidazolium (CMZ), an inhibitor of CaM, was added to the pipette solution (pCa of 6.5 or 300 n<i>M<\/i> [Ca]<sub>i<\/sub>). The amplitude of maximally activated I<sub>Ba<\/sub> was \u20134.3 \u00b1 0.5 pA\/pF (n = 13) for control and \u20138.1 \u00b1 0.9 pA\/pF (n = 14) in the presence of CMZ. This difference was statistically significant (p = 0.016). The CMZ stimulation of I<sub>Ba<\/sub> was not abolished when 5 \u00b5<i>M<\/i> KN-62, a specific inhibitor of CaMK-II, was included in the pipette (\u20139.5 \u00b1 1.1 pA\/pF; n = 10). Introduction of CaMK-II itself intracellularly had no effect on the basal I<sub>Ba<\/sub>. On the other hand, the CMZ stimulation of I<sub>Ba<\/sub> was prevented by both H-7, a nonspecific protein kinase inhibitor, and H-89, a specific inhibitor of protein kinase A (PK-A). Since CMZ is a strong inhibitor of Ca<sup>2+<\/sup>\/CaM-dependent phosphodiesterase (type I PDE), we studied the effect of 8-methoxymethyl-3-isobutyl-1-methylxanthine (MIBMX), another specific inhibitor of the PDE. MIBMX, like CMZ, stimulated I<sub>Ba<\/sub>: control, \u20134.6 \u00b1 0.4 pA\/pF (n = 10); MIBMX, \u20139.6 \u00b1 1.2 (n = 8), and CMZ, \u20137.9 \u00b1 0.9 (n = 15). 0.1 m<i>M<\/i> 8Br-cAMP, a membrane permeable cAMP analogue, stimulated I<sub>Ba<\/sub> by +42%: before, \u20133.7 \u00b1 0.7 pA\/pF; after, \u20135.2 \u00b1 1.0 (n = 6). In conclusion, Ca<sup>2+<\/sup> channels of VSM cells might not be directly regulated by the CaM\/CaMK-II pathway. Therefore, the CMZ stimulation of I<sub>Ba<\/sub> might occur due to the increase in intracellular concentration of cAMP produced by inhibition of CaM-dependent PDE.<\/jats:p>","DOI":"10.1159\/000025599","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T09:24:25Z","timestamp":1050398665000},"page":"303-309","source":"Crossref","is-referenced-by-count":13,"title":["Intracellular Application of Calmidazolium Increases Ca<sup>2+<\/sup> Current through Activation of Protein Kinase A in Cultured Vascular Smooth Muscle Cells"],"prefix":"10.1159","volume":"35","author":[{"given":"Masanori","family":"Sunagawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisashi","family":"Yokoshiki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Seki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Sperelakis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[1998,10,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(87)90003-3"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050281"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1038\/357074a0"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.5.2506"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(95)02096-9"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(89)90631-X"}],"container-title":["Journal of Vascular Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/25599","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/25599","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T03:49:46Z","timestamp":1745466586000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000025599"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998]]},"references-count":6,"journal-issue":{"issue":"5","published-online":{"date-parts":[[1998,10,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000025599","archive":["Portico"],"relation":{},"ISSN":["1018-1172","1423-0135"],"issn-type":[{"value":"1018-1172","type":"print"},{"value":"1423-0135","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998]]}}}