Cerebellar granule cell GABA(A) receptors studied at the single-channel level: modulation by protein kinase G.

Rat cerebellar granule cells GABA(A) receptors were studied at the single-channel level in outside-out patches. Three conductance levels were detected as activated by 0.1 microM GABA: 11, 20 and 30 pS. Single-channel I-V relationships were linear. The probability of opening did not vary over time within 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 time 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 not affect single-channel conductances, but resulted in a reduction over time of single-channel open probability for all the conductance levels. Kinetically, protein kinase G modified the mean open time constants and the relative areas of the two components of the closed state distribution whereas the mean closed time constants remained unaffected. These results confirm and add details about cerebellar granule GABA(A) receptors down regulation by PKG.