{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T22:24:35Z","timestamp":1771626275017,"version":"3.50.1"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[1996,6]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>\u03b1-Adrenergic receptor stimulation regulates the activity of a number of different cardiac ion channels, including those underlying one or more distinct Cl<jats:sup>\u2212<\/jats:sup>conductances. The whole-cell patch-clamp technique was used in the present study to investigate the effects of \u03b1-adrenergic stimulation on the \u03b2-adrenergically regulated Cl<jats:sup>\u2212<\/jats:sup>current in guinea pig ventricular myocytes. Neither \u03b1<jats:sub>1<\/jats:sub>-adrenergic receptor stimulation with methoxamine (25 to 500 \u03bcmol\/L) nor direct activation of endogenous protein kinase C (PKC) with phorbol 12,13-dibutyrate (PDBu, 100 nmol\/L) evoked a Cl<jats:sup>\u2212<\/jats:sup>current. On the contrary, the Cl<jats:sup>\u2212<\/jats:sup>current activated by 30 nmol\/L isoproterenol was inhibited by methoxamine, with an EC<jats:sub>50<\/jats:sub>of 6.7\u00b12.6 \u03bcmol\/L, and this response was blocked by prazosin, an \u03b1<jats:sub>1<\/jats:sub>-adrenergic receptor antagonist. Prazosin also decreased the EC<jats:sub>50<\/jats:sub>for current activation by norepinephrine from 53\u00b17.1 to 18\u00b13.8 nmol\/L, demonstrating that the ability of this endogenous neurotransmitter to activate the Cl<jats:sup>\u2212<\/jats:sup>current through \u03b2-adrenergic receptor stimulation is limited by its intrinsic ability to also activate \u03b1-adrenergic receptors. Methoxamine did not inhibit the Cl<jats:sup>\u2212<\/jats:sup>current evoked by either direct activation of adenylate cyclase with forskolin or inhibition of phosphodiesterase activity with 3-isobutyl-1-methylxanthine, indicating that \u03b1-adrenergic stimulation inhibits \u03b2-adrenergic responses at a point upstream of adenylate cyclase activation. Methoxamine also did not inhibit the Cl<jats:sup>\u2212<\/jats:sup>current activated by histamine, suggesting that \u03b1-adrenergic stimulation specifically inhibits \u03b2-adrenergic receptor\u2013mediated responses. The inhibitory effect of methoxamine was not mimicked by PDBu, and it persisted in the presence of bisindolylmaleimide, a selective PKC inhibitor. However, methoxamine inhibition of the isoproterenol-activated Cl<jats:sup>\u2212<\/jats:sup>current was sensitive to pertussis toxin. These results suggest that \u03b1-adrenergic receptor stimulation inhibits the \u03b2-adrenergically activated Cl<jats:sup>\u2212<\/jats:sup>current, demonstrating a novel mechanism by which \u03b1-adrenergic receptors may regulate ion channel activity in the heart.<\/jats:p>","DOI":"10.1161\/01.res.78.6.1090","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:47:05Z","timestamp":1339462025000},"page":"1090-1099","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["\u03b1<sub>1<\/sub>-Adrenergic Inhibition of the \u03b2-Adrenergically Activated Cl<sup>\u2212<\/sup>Current in Guinea Pig Ventricular Myocytes"],"prefix":"10.1161","volume":"78","author":[{"given":"Lisa M.","family":"Oleksa","sequence":"first","affiliation":[{"name":"From the Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Livia C.","family":"Hool","sequence":"additional","affiliation":[{"name":"From the Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert D.","family":"Harvey","sequence":"additional","affiliation":[{"name":"From the Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1993.73.2.469"},{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0031-6997(25)00447-8","volume":"45","year":"1993","unstructured":"Terzic A, Puc\u00e9at M, Vassort G, Vogel SM. 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