Inhibition of L-type calcium channels by internal GTP [gamma S] in mouse pancreatic beta cells.
Pretreatment of pancreatic beta cells with pertussis toxin resulted in a 30% increase in peak whole-cell Ca2+ currents recorded in the absence of exogenous intracellular guanine nucleotides. Intracellular application of 90 microM GTP[gamma S], by liberation from a caged precursor, resulted in 40% reduction of the peak Ca2+ current irrespective of whether the current was carried by Ca2+ or Ba2+. Effects on the delayed outward K+ current were small and restricted to a transient Ca(2+)-dependent K+ current component. Inhibition by GTP[gamma S] of the Ca2+ current was not mimicked by standard GTP and could not be prevented either by pretreatment with pertussis toxin or by inclusion of GDP[beta S] or cyclic AMP in the intracellular medium. The inhibitory effect of GTP[gamma S] could be counteracted by a prepulse to a large depolarizing voltage. A similar effect of a depolarizing prepulse was observed in control cells with no exogenous guanine nucleotides. These observations indicate that inhibition of beta cell Ca2+ current by G protein activation results from direct interaction with the channel and does not involve second-messenger systems. Our findings also suggest that the beta cell Ca2+ current is subject to resting inhibition by G proteins.
Ammälä
C
C
Department of Medical Physics, Gothenburg University, Sweden.
Berggren
P O
PO
Bokvist
K
K
Rorsman
P
P
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007425:Intracellular Membranes; D007515:Islets of Langerhans / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D037342:Pertussis Toxin; D011188:Potassium / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015220:Calcium Channels; D010566:Virulence Factors, Bordetella; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D011188:Potassium