BACLOFEN INHIBITION OF THE HYPERPOLARIZATION-ACTIVATED CATION CURRENT, I-H, IN RAT SUBSTANTIA-NIGRA ZONA COMPACTA NEURONS MAY BE SECONDARY TO POTASSIUM CURRENT ACTIVATION
Ae. Watts et al., BACLOFEN INHIBITION OF THE HYPERPOLARIZATION-ACTIVATED CATION CURRENT, I-H, IN RAT SUBSTANTIA-NIGRA ZONA COMPACTA NEURONS MAY BE SECONDARY TO POTASSIUM CURRENT ACTIVATION, Journal of neurophysiology, 76(4), 1996, pp. 2262-2270
1. The properties of the hyperpolarization-activated cation current (I
-h), and its modulation by gamma-aminobuturic acid-B (GABA(B)) recepto
r activation and protein kinase A, were investigated using whole cell
voltage clamp of substantia nigra zona compacta principal neurons in r
at midbrain slices in vitro. 2. At 30 degrees C, I-h activated between
-75 and -155 mV, with a V-1/2 of -115 mV. At 35 degrees C, the activa
tion curve shifted positive by 10 mV. I-h had an estimated reversal po
tential of -27 mV. Ion substitution experiments showed that the curren
t was carried by Na+ and K+. 3. Application of the GABA(B) receptor ag
onist baclofen (30 mu M) induced an outward potassium current (G(IRK))
, increased neuronal membrane conductance and inhibited I-h. The inhib
ition of I-h was voltage independent. Baclofen induced an 11-mV positi
ve shift in the reversal potential of I-h. 4. Extracellular barium (30
0 mu M) markedly reduced the baclofen-evoked outward current and assoc
iated increase in membrane conductance due to G(IRK) activation. There
was also very little inhibition of I-h by baclofen in the presence of
barium. When cesium was the major intracellular cation, both the incr
ease in membrane conductance due to G(IRK) activation and the inhibiti
on of I-h evoked by baclofen were reduced by a similar extent. 5. Neit
her forskolin (10 mu M) nor the protein kinase A inhibitor, H89 (10 mu
M), had any effect on I-h or its inhibition by baclofen. 6. These dat
a suggest that the inhibition of I-h by baclofen is secondary to the a
ctivation of G(IRK), i.e., due directly to alteration of membrane cond
uctance, rather than a distinct effect, and is not mediated by inhibit
ion of adenylyl cyclase.