[PDF][PDF] Significance of Na/Ca exchange for Ca2+ buffering and electrical activity in mouse pancreatic β-cells

D Gall, J Gromada, I Susa, P Rorsman, A Herchuelz… - Biophysical journal, 1999 - cell.com
D Gall, J Gromada, I Susa, P Rorsman, A Herchuelz, K Bokvist
Biophysical journal, 1999cell.com
We have combined the patch-clamp technique with microfluorimetry of the cytoplasmic Ca
2+ concentration ([Ca 2+] i) to characterize Na/Ca exchange in mouse β-cells and to
determine its importance for [Ca 2+] i buffering and shaping of glucose-induced electrical
activity. The exchanger contributes to Ca 2+ removal at [Ca 2+] i above 1μM, where it
accounts for> 35% of the total removal rate. At lower [Ca 2+] i, thapsigargin-sensitive Ca 2+-
ATPases constitute a major (70% at 0.8μM [Ca 2+] i) mechanism for Ca 2+ removal. The β …
Abstract
We have combined the patch-clamp technique with microfluorimetry of the cytoplasmic Ca2+ concentration ([Ca2+]i) to characterize Na/Ca exchange in mouse β-cells and to determine its importance for [Ca2+]i buffering and shaping of glucose-induced electrical activity. The exchanger contributes to Ca2+ removal at [Ca2+]i above 1μM, where it accounts for >35% of the total removal rate. At lower [Ca2+]i, thapsigargin-sensitive Ca2+-ATPases constitute a major (70% at 0.8μM [Ca2+]i) mechanism for Ca2+ removal. The β-cell Na/Ca exchanger is electrogenic and has a stoichiometry of three Na+ for one Ca2+. The current arising from its operation reverses at ∼−20mV (current inward at more negative voltages), has a conductance of 53 pS/pF (14μM [Ca2+]i), and is abolished by removal of external Na+ or by intracellularly applied XIP (exchange inhibitory peptide). Inhibition of the exchanger results in shortening (50%) of the bursts of action potentials of glucose-stimulated β-cells in intact islets and a slight (5mV) hyperpolarization. Mathematical simulations suggest that the stimulatory action of glucose on β-cell electrical activity may be accounted for in part by glucose-induced reduction of the cytoplasmic Na+ concentration with resultant activation of the exchanger.
cell.com