Cerebellar granule cell GABA, receptors studied at the single-channel level: Modulation by protein kinase G

Rat cerebellar granule cells GABA(A) receptors were studied at the single-c hannel level in outside-out patches. Three conductance levels were detected as activated by 0.1 mu M GABA: 11, 20 and 30 pS. Single-channel I-V relati onships were linear. The probability of opening did not vary over time with in single patches. Kinetic analysis brought to a mean open time constant of 3.2, 2.9 and 2.8 ms respectively for each conductance level and a closed t ime histogram fitted by the sum of two exponential functions ( tau(c1) = 2. 1 ms, 43%; tau(c2) = 18.2 ms, 57%). Protein kinase G (PKG) activation did n ot affect single-channel conductances, but resulted in a reduction over tim e of single-channel open probability for all the conductance levels. Kineti cally, protein kinase G; modified the mean open time constants and the rela tive areas of the two components of the closed state distribution whereas t he mean closed time constants remained unaffected. These results confirm an d add details about cerebellar granule GABA(A) receptors down regulation by PKG. (C) 1998 Academic Press.