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This Article Full Text Full Text (PDF) All Versions of this Article: 294/6/E1178    most recent 90237.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Tian, Y. Articles by Moitoso de Vargas, L. Search for Related Content PubMed PubMed Citation Articles by Tian, Y. Articles by Moitoso de Vargas, L.

Differential modulation of L-type calcium channel subunits by oleate

¹Department of Pharmacology and Toxicology, Virginia Commonwealth University Medical Center, Richmond, Virginia; and ²Division of Molecular Medicine and Obesity Research Center, Boston Medical Center, Boston, Massachusetts

Submitted 14 February 2008 ; accepted in final form 15 April 2008

Nonesterified fatty acids such as oleate and palmitate acutely potentiate insulin secretion from pancreatic islets in a glucose-dependent manner. In addition, recent studies show that fatty acids elevate intracellular free Ca²⁺ and increase voltage-gated Ca²⁺ current in mouse β-cells, although the mechanisms involved are poorly understood. Here we utilized a heterologous system to express subunit-defined voltage-dependent L-type Ca²⁺ channels (LTCC) and demonstrate that β-cell calcium may increase in part from an interaction between fatty acid and specific calcium channel subunits. Distinct functional LTCC were assembled in both COS-7 and HEK-293 cells by expressing either one of the EYFP-tagged L-type ₁-subunits (β-cell Cav1.3 or lung Cav1.2) and ERFP-tagged islet β-subunits (iβ_2a or iβ₃). In COS-7 cells, elevations in intracellular Ca²⁺ mediated by LTCC were enhanced by an oleate-BSA complex. To extend these findings, Ca²⁺ current was measured in LTCC-expressing HEK-293 cells that revealed an increase in peak Ca²⁺ current within 2 min after addition of the oleate complex, with maximal potentiation occurring at voltages <0 mV. Both Cav1.3 and Cav1.2 were modulated by oleate, and the presence of different auxiliary β-subunits resulted in differential augmentation. The potentiating effect of oleate on Cav1.2 was abolished by the pretreatment of cells with triacsin C, suggesting that long-chain CoA synthesis is necessary for Ca²⁺ channel modulation. These results show for the first time that two L-type Ca²⁺ channels expressed in β-cells (Cav1.3 and Cav1.2) appear to be targeted by nonesterified fatty acids. This effect may account in part for the acute potentiation of glucose-dependent insulin secretion by fatty acids.

β-cell calcium; free fatty acids; insulin secretion

This article has been cited by other articles:

				K. S. Gwiazda, T.-L. B. Yang, Y. Lin, and J. D. Johnson Effects of palmitate on ER and cytosolic Ca2+ homeostasis in {beta}-cells Am J Physiol Endocrinol Metab, April 1, 2009; 296(4): E690 - E701. [Abstract] [Full Text] [PDF]