| Autor: |
Vignali, Sheila, Leiss, Veronika, Karl, Rosi, Hofmann, Franz, Welling, Andrea |
| Předmět: |
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| Zdroj: |
Journal of Physiology; May2006, Vol. 572 Issue 3, p691-706, 16p, 2 Charts, 5 Graphs |
| Abstrakt: |
Insulin and glucagon are the major hormones of the islets of Langerhans that are stored and released from the B- and A-cells, respectively. Both hormones are secreted when the intracellular cytosolic Ca2+ concentration ([Ca2+]i) increases. The [Ca2+]i is modulated by mutual inhibition and activation of different voltage-gated ion channels. The precise interplay of these ion channels in either glucagon or insulin release is unknown, owing in part to the difficulties in distinguishing A- from B-cells in electrophysiological experiments. We have established a single-cell RT-PCR method to identify A- and B-cells from the mouse. A combination of PCR, RT-PCR, electrophysiology and pharmacology enabled us to characterize the different sodium and calcium channels in mouse islet cells. In both A- and B-cells, 60% of the inward calcium current ( ICa) is carried by L-type calcium channels. In B-cells, the predominant calcium channel is CaV1.2, whereas CaV1.2 and CaV1.3 were identified in A-cells. These results were confirmed by using mice carrying A- or B-cell-specific inactivation of the CaV1.2 gene. In B-cells, the remaining ICa flows in equal amounts through CaV2.1, CaV2.2 and CaV2.3. In A-cells, 30 and 15% of ICa is due to CaV2.3 and CaV2.1 activity, respectively, whereas CaV2.2 current was not found in these cells. Low-voltage-activated T-type calcium channels could not be identified in A- and B-cells. Instead, two TTX-sensitive sodium currents were found: an early inactivating and a residual current. The residual current was only recovered in a subpopulation of B-cells. A putative genetic background for these currents is NaV1.7. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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