Effect of substitution of a permeable weak acid for the permissive role of glucose in amino acid-induced electrical activity in B-cells.
The amino acids L-leucine, L-isoleucine, and L-arginine require a subthreshold concentration of glucose to elicit insulin release and electrical activity from B-cells. There is evidence suggesting that protons couple the metabolism of glucose to the functional response of B-cells. In view of this, a permeable weak acid, sulfamerazine, was used to determine if the generation of intracellular protons could account for the permissive action of glucose. Addition of 10 mM sulfamerazine elicited constant spike activity only with 20 mM leucine. With 20 mM arginine or isoleucine, sulfamerazine induced silent depolarization no different from that caused by sulfamerazine alone. The pattern of the electrical activity of each amino acid plus 5.6 mM glucose or alpha-ketoisocaproic acid alone was qualitatively different; addition of sulfamerazine enhanced the electrical response. The permeable weak base NH4Cl at 20 mM immediately inhibited the electrical response to each amino acid plus glucose or alpha-ketoisocaproic acid alone. The effects of the permeable weak acid and base indicate that intracellular pH is important in maintaining amino acid-induced electrical activity. The permissive role of glucose may be due to provision of protons only with leucine.
D000200:Action Potentials / Q000187:drug effects; D000596:Amino Acids / Q000502:physiology*; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002463:Cell Membrane Permeability; D004357:Drug Synergism; D005947:Glucose / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000502:physiology*; D007651:Keto Acids / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D013416:Sulfamerazine / Q000494:pharmacology*
D000596:Amino Acids; D007651:Keto Acids; D000643:Ammonium Chloride; D005947:Glucose; D013416:Sulfamerazine