Gamma-aminobutyric acid modulates chloride channel activity in cultured primary bovine lactotrophs.
The effects of GABA, the analogues muscimol and baclofen, and the antagonist bicuculline were investigated on cultured primary bovine lactotrophs using the patch clamp technique. Under voltage clamp in the whole cell mode using solutions containing chloride as the only permeable ion, GABA application increased the amplitude of mean membrane current and fluctuations of current about this mean. Statistical analysis of current fluctuations induced by GABA showed that the power density spectra in 8 of 12 cells were best fitted to double Lorentzian functions and the variance was smallest around the estimated equilibrium potential of chloride ions. The underlying channel open time estimated from noise analysis was only weakly voltage-dependent. The variance of current noise increased with GABA concentration within the range of 1-30 microM, although a slight decrease of variance in one cell could be observed at 30 microM, suggesting that desensitization to GABA might occur. Muscimol mimicked the effect of GABA but baclofen was without effect under these conditions. Bicuculline reduced the GABA-activated membrane current fluctuations. GABA- or muscimol-activated channels recorded in isolated outside-out patches had a slope conductance of about 20 pS. Mean open times of the channel were characterized by two exponential decay functions. We conclude that bovine lactotrophs have GABA-activated chloride channels, which appear to be voltage-independent. In addition, the action of GABA appears to be mediated through the GABAA receptor subtype.
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011388:Prolactin / Q000378:metabolism* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D002712:Chlorides; D007473:Ion Channels; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D011388:Prolactin; D001640:Bicuculline