The effects of nitric oxide on the membrane potential and ionic currents of mouse pancreatic B cells.
Nitric oxide (NO) is considered to contribute to the impairment of B cell function in insulin-dependent diabetes mellitus. The effects of compounds that release NO were tested on the membrane potential and ionic currents of mouse pancreatic B cells using intracellular microelectrodes and the whole-cell patch-clamp technique. S-Nitrosocysteine led to a concentration-dependent reduction of electrical activity induced by 15 mM glucose. At a concentration of 1 mM, S-nitrosocysteine cause a hyperpolarization of the plasma membrane with complete suppression of electrical activity. In about half of the cells tested, electrical activity reappeared during treatment with S-nitroso-cysteine or after wash-out. However, in the other cells the hyperpolarization was followed by a slow depolarization and electrical activity did not reappear. The perforated-patch whole-cell K+ATP current first increased and subsequently decreased again during exposure to 1 mM S-nitroso-cysteine. With 0.1 and 0.01 mM S-nitroso-cysteine, only the rise of the current amplitude was observed. S-nitroso-cysteine (1 mM) almost completely abolished the current through voltage-dependent Ca2+ channels (measured with Ba2+ as charge carrier). Like S-nitroso-cysteine, 100 microM sodium-nitroprusside, another donor, evoked a marked hyperpolarization of the membrane potential that was at least in part reversible. To further ascertain that the effect of S-nitroso-cysteine was mediated by NO, we tested the decomposition products of S-nitroso-cysteine. Nitrite and denitrosylated S-nitroso-cystein (1 mM) did not alter electrical activity of B cells, whereas cysteine (1 mM) caused a slight depolarization. It is concluded that exogenous NO evokes rapid changes of B cell function by influencing the activity of ion channels.
Krippeit-Drews
P
P
Department of Physiology, University of Tübingen, Germany.
Kröncke
K D
KD
Welker
S
S
Zempel
G
G
Roenfeldt
M
M
Ammon
H P
HP
Lang
F
F
Drews
G
G
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D026403:S-Nitrosothiols
D015220:Calcium Channels; D015221:Potassium Channels; D026403:S-Nitrosothiols; D009599:Nitroprusside; D009569:Nitric Oxide; C021315:S-nitrosocysteine; D003545:Cysteine