Gi2 proteins couple somatostatin receptors to low-conductance K+ channels in rat pancreatic alpha-cells.
Somatostatin hyperpolarized rat pancreatic alpha-cells and inhibited spontaneous electrical activity by activating a low-conductance K+ channel (0.9 pS with physiological ionic gradients). This channel was insensitive to tolbutamide (a blocker of ATP-sensitive K+ channels) and apamin (an inhibitor of small-conductance Ca(2+)-activated K+ channels). Channel activation was prevented by pre-treating the cells with pertussis toxin, indicating the involvement of G-proteins. A direct interaction between an inhibitory G-protein and the somatostatin-activated K+ channel is suggested by the finding that intracellular application of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma-S) and the G beta gamma subunit of G-proteins resulted in a transient stimulation of the current. Activation of the K+ current by somatostatin was inhibited by intracellular dialysis with specific antibodies to Gi1/2 and was not seen in cells treated with antisense oligonucleotides against G-proteins of the subtype Gi2. We conclude that somatostatin suppresses alpha-cell electrical activity by a Gi2-protein-dependent mechanism, which culminates in the activation of a sulphonylurea- and apamin-insensitive low-conductance K+ channel.
Gromada
J
J
Novo Nordisk A/S, Novo Alle, 2880 Bagsvaerd, Denmark. jesper_gromada@lilly.com
Høy
M
M
Olsen
H L
HL
Gotfredsen
C F
CF
Buschard
K
K
Rorsman
P
P
Bokvist
K
K
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003956:Dialysis; D004553:Electric Conductivity; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000276:immunology / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007515:Islets of Langerhans / Q000502:physiology*; D008297:Male; D037342:Pertussis Toxin; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D017481:Receptors, Somatostatin / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000906:Antibodies; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D017481:Receptors, Somatostatin; D010566:Virulence Factors, Bordetella; D001030:Apamin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013004:Somatostatin; D014044:Tolbutamide; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D002118:Calcium