MODULATION BY DIFFERENT GABA(B) RECEPTOR TYPES OF VOLTAGE-ACTIVATED CALCIUM CURRENTS IN RAT THALAMOCORTICAL NEURONS

1. The effects of the GABA(B) receptor agonist baclofen on the voltage-dependent Ca2+ currents were studied in rat thalamocortical neurones with the use of whole cell voltage-clamp recordings in brain slices. 2. The contribution of N-, L- and P-types of Ca2+ channels to the total high voltage-activated Ca2+ (HVA Ca2+) current was assessed by the use of omega-conotoxin, nifedipine and omega-agatoxin IVA, respectively. No P-type current could be detected. Thus, the HVA Ca2+ current contained an N- and an L-type current (23 and 15% of the total current, respectively) and a residual current, which will be referred to as the 'R' component. 3. Baclofen (1-50 mu M) had no effect on the low voltage-activated (LVA) Ca2+ current (I-T). 4. At low concentrations (0.5-10 mu M), baclofen decreased the HVA Ca2+ currents by about 10-20% without a marked modification on the kinetics, whereas 50 mu M baclofen decreased the HVA Ca2+ currents by about 40% with a pronounced slowing down of the kinetics. 5. The 10-20% decrease of the total HVA Ca2+ currents produced by the low concentrations of baclofen occurred as the result of a 30% block of the 'R' component. The additional decrease observed with the dose of 50 mu M was due to a full block of the N-type current. The L-type was unaffected by baclofen. 6. The effect of baclofen on the total HVA Ca2+ current was partially blocked by GABA(B) receptor antagonists indicating that it occurred through stimulation of GABA(B) receptors. 7. The effect of baclofen on the N-type current was abolished by CGP 35348 (100 mu M) and CGP 55845A (100 nM). The effect on the 'R' component was also antagonized by CGP 55845A (100 nM) although with a lower potency, but was not blocked by CGP 35348 (100 mu M). 8. We conclude that the effects of baclofen on the various components of the HVA Ca2+ currents occur through different types of GABA(B) receptors. One receptor has a high affinity for baclofen (i.e. saturated by concentrations as low as 0.5 mu M), is insensitive to CGP 35348, is coupled to the 'R' component and is responsible for a maximum 20% decrease in the total HVA Ca2+ current. The other receptor has a lower affinity for baclofen (i.e. affected by a concentration of 50 mu M), is sensitive to CGP 35348, is coupled to the N-type Ca2+ current and is responsible for the additional 20-30% decrease in the HVA Ca2+ current observed with 50 mu M baclofen.