دورية أكاديمية
Phosphorylation-dependent modulation of cardiac calcium current by intracellular free magnesium.
| العنوان: | Phosphorylation-dependent modulation of cardiac calcium current by intracellular free magnesium. |
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| المؤلفون: | Pelzer S; Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7., La C, Pelzer DJ |
| المصدر: | American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2001 Oct; Vol. 281 (4), pp. H1532-44. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901228 Publication Model: Print Cited Medium: Print ISSN: 0363-6135 (Print) Linking ISSN: 03636135 NLM ISO Abbreviation: Am J Physiol Heart Circ Physiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, Md. : American Physiological Society, |
| مواضيع طبية MeSH: | Calcium Channels/*physiology , Intracellular Membranes/*metabolism , Magnesium/*physiology , Myocardium/*metabolism, Animals ; Carbazoles/pharmacology ; Cyclic AMP/pharmacology ; Electric Conductivity ; Enzyme Inhibitors/pharmacology ; Female ; Guinea Pigs ; Indole Alkaloids ; Male ; Myocardium/cytology ; Phosphorylation ; Protein Kinase Inhibitors ; Protein Kinases/physiology |
| مستخلص: | We compared the effects of cytosolic free magnesium (Mg(2+)(i)) on L-type Ca(2+) current (I(Ca,L)) in patch-clamped guinea pig ventricular cardiomyocytes under basal conditions, after inhibition of protein phosphorylation, and after stimulation of cAMP-mediated phosphorylation. Basal I(Ca,L) density displayed a bimodal dependence on the concentration of Mg(2+)(i) ([Mg(2+)](i); 10(-6)-10(-2) M), which changed significantly as cell dialysis progressed due to a pronounced and long-lasting rundown of I(Ca,L) in low-Mg(2+) dialysates. Ten minutes after patch breakthrough, I(Ca,L) density (at +10 mV) in Mg(2+)(i)-depleted cells ([Mg(2+)](i) approximately 1 microM) was elevated, increased to a maximum at approximately 20 microM [Mg(2+)](i), and declined steeply at higher [Mg(2+)](i). Treatment with the broad-spectrum protein kinase inhibitor K252a (10 microM) reduced I(Ca,L) density and abolished these effects of Mg(2+)(i) except for a negative shift of I(Ca,L)-voltage relations with increasing [Mg(2+)](i). Maximal stimulation of cAMP-mediated phosphorylation occluded the Mg(2+)(i)-induced stimulation of I(Ca,L) and prevented inhibitory effects of the ion at [Mg(2+)](i) <1 mM but not at higher concentrations. These results show that the modulation of I(Ca,L) by Mg(2+)(i) requires protein kinase activity and likely originates from interactions of the ion with proteins involved in the regulation of protein phosphorylation/dephosphorylation. Stimulatory effects of Mg(2+)(i) on I(Ca,L) seem to increase the cAMP-mediated phosphorylation of Ca(2+) channels, whereas inhibitory effects of Mg(2+)(i) appear to curtail and/or reverse cAMP-mediated phosphorylation. |
| المشرفين على المادة: | 0 (Calcium Channels) 0 (Carbazoles) 0 (Enzyme Inhibitors) 0 (Indole Alkaloids) 0 (Protein Kinase Inhibitors) 97161-97-2 (staurosporine aglycone) E0399OZS9N (Cyclic AMP) EC 2.7.- (Protein Kinases) I38ZP9992A (Magnesium) |
| تواريخ الأحداث: | Date Created: 20010915 Date Completed: 20011025 Latest Revision: 20200930 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1152/ajpheart.2001.281.4.H1532 |
| PMID: | 11557541 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0363-6135 |
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| DOI: | 10.1152/ajpheart.2001.281.4.H1532 |