{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:33:57Z","timestamp":1791408837082,"version":"4.3.3"},"reference-count":36,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,22]],"date-time":"2024-12-22T00:00:00Z","timestamp":1734825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Flexi Funds Programme of Forschungscampus Mittelhessen (FCMH)","award":["Projektnummer 2018_1_1_2"],"award-info":[{"award-number":["Projektnummer 2018_1_1_2"]}]},{"name":"Flexi Funds Programme of Forschungscampus Mittelhessen (FCMH)","award":["DFG WO 1732\/4-2"],"award-info":[{"award-number":["DFG WO 1732\/4-2"]}]},{"name":"Flexi Funds Programme of Forschungscampus Mittelhessen (FCMH)","award":["DFG-Projektnummer 521379614"],"award-info":[{"award-number":["DFG-Projektnummer 521379614"]}]},{"name":"DFG-Forschergruppe \u201cNeurobiology of affective disorders: Translational perspectives on brain structure and function\u201d (FOR 2107)","award":["Projektnummer 2018_1_1_2"],"award-info":[{"award-number":["Projektnummer 2018_1_1_2"]}]},{"name":"DFG-Forschergruppe \u201cNeurobiology of affective disorders: Translational perspectives on brain structure and function\u201d (FOR 2107)","award":["DFG WO 1732\/4-2"],"award-info":[{"award-number":["DFG WO 1732\/4-2"]}]},{"name":"DFG-Forschergruppe \u201cNeurobiology of affective disorders: Translational perspectives on brain structure and function\u201d (FOR 2107)","award":["DFG-Projektnummer 521379614"],"award-info":[{"award-number":["DFG-Projektnummer 521379614"]}]},{"name":"DFG-Sonderforschungsbereich\/Transregio \u201cTrajectories of affective disorders: Cognitive-emotional mechanisms of symptom change\u201d (SFB\/TRR 393)","award":["Projektnummer 2018_1_1_2"],"award-info":[{"award-number":["Projektnummer 2018_1_1_2"]}]},{"name":"DFG-Sonderforschungsbereich\/Transregio \u201cTrajectories of affective disorders: Cognitive-emotional mechanisms of symptom change\u201d (SFB\/TRR 393)","award":["DFG WO 1732\/4-2"],"award-info":[{"award-number":["DFG WO 1732\/4-2"]}]},{"name":"DFG-Sonderforschungsbereich\/Transregio \u201cTrajectories of affective disorders: Cognitive-emotional mechanisms of symptom change\u201d (SFB\/TRR 393)","award":["DFG-Projektnummer 521379614"],"award-info":[{"award-number":["DFG-Projektnummer 521379614"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>CACNA1C encodes the \u03b11c subunit of the L-type Ca2+ channel, Cav1.2. Ventricular myocytes from haploinsufficient Cacna1c (Cacna1c+\/\u2212) rats exhibited reduced expression of Cav1.2 but an apparently normal sarcolemmal Ca2+ influx with an impaired response to sympathetic stress. We tested the hypothesis that the altered phosphorylation of Cav1.2 might underlie the sarcolemmal Ca2+ influx phenotype in Cacna1c+\/\u2212 myocytes using immunoblotting of the left ventricular (LV) tissue from Cacna1c+\/\u2212 versus wildtype (WT) hearts. Activation of cAMP-dependent protein kinase A (PKA) increases L-type Ca2+ current and phosphorylates Cav1.2 at serine-1928. Using an antibody directed against this phosphorylation site, we observed elevated phosphorylation of Cav1.2 at serine-1928 in LV myocardium from Cacna1c+\/\u2212 rats under basal conditions (+110% versus WT). Sympathetic stress was simulated by isoprenaline (100 nM) in Langendorff-perfused hearts. Isoprenaline increased the phosphorylation of serine-1928 in Cacna1c+\/\u2212 LV myocardium by \u2248410%, but the increase was significantly smaller than in WT myocardium (\u2248650%). In conclusion, our study reveals altered PKA-dependent phosphorylation of Cav1.2 with elevated phosphorylation of serine-1928 under basal conditions and a diminished phosphorylation reserve during \u03b2-adrenergic stimulation. These alterations in the phosphorylation of Cav1.2 may explain the apparently normal sarcolemmal Ca2+ influx in Cacna1c+\/\u2212 myocytes under basal conditions as well as the impaired response to sympathetic stimulation.<\/jats:p>","DOI":"10.3390\/ijms252413713","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T04:33:29Z","timestamp":1734928409000},"page":"13713","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Altered Protein Kinase A-Dependent Phosphorylation of Cav1.2 in Left Ventricular Myocardium from Cacna1c Haploinsufficient Rat Hearts"],"prefix":"10.3390","volume":"25","author":[{"given":"David","family":"K\u00f6nigstein","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Biochemical and Pharmacological Center (BPC) Marburg, University of Marburg, 35032 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1092-0591","authenticated-orcid":false,"given":"Hauke","family":"Fender","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Biochemical and Pharmacological Center (BPC) Marburg, University of Marburg, 35032 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Pla\u010dki\u0107","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Biochemical and Pharmacological Center (BPC) Marburg, University of Marburg, 35032 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9010-9568","authenticated-orcid":false,"given":"Theresa M.","family":"Kisko","sequence":"additional","affiliation":[{"name":"Center for Mind, Brain and Behavior (CMBB), University of Marburg, 35032 Marburg, Germany"},{"name":"Behavioral Neuroscience, Experimental and Biological Psychology, University of Marburg, 35032 Marburg, Germany"},{"name":"KU Leuven, Faculty of Psychology and Educational Sciences, Research Unit Brain and Cognition, Laboratory of Biological Psychology, Social and Affective Neuroscience Research Group, B-3000 Leuven, Belgium"},{"name":"KU Leuven, Leuven Brain Institute, B-3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6986-5684","authenticated-orcid":false,"given":"Markus","family":"W\u00f6hr","sequence":"additional","affiliation":[{"name":"Center for Mind, Brain and Behavior (CMBB), University of Marburg, 35032 Marburg, Germany"},{"name":"Behavioral Neuroscience, Experimental and Biological Psychology, University of Marburg, 35032 Marburg, Germany"},{"name":"KU Leuven, Faculty of Psychology and Educational Sciences, Research Unit Brain and Cognition, Laboratory of Biological Psychology, Social and Affective Neuroscience Research Group, B-3000 Leuven, Belgium"},{"name":"KU Leuven, Leuven Brain Institute, B-3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0131-4338","authenticated-orcid":false,"given":"Jens","family":"Kocksk\u00e4mper","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Biochemical and Pharmacological Center (BPC) Marburg, University of Marburg, 35032 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109262","DOI":"10.1016\/j.neuropharm.2022.109262","article-title":"CACNA1C (Ca(V)1.2) and other L-type calcium channels in the pathophysiology and treatment of psychiatric disorders: Advances from functional genomics and pharmacoepidemiology","volume":"220","author":"Harrison","year":"2022","journal-title":"Neuropharmacology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.cell.2004.09.011","article-title":"Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism","volume":"119","author":"Splawski","year":"2004","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.yjmcc.2015.01.002","article-title":"Gain-of-function mutations in the calcium channel CACNA1C (Cav1.2) cause non-syndromic long-QT but not Timothy syndrome","volume":"80","author":"Wemhoner","year":"2015","journal-title":"J. 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