Baclofen inhibition of the hyperpolarization-activated cation current, I(h), in rat substantia nigra zona compacta neurons may be secondary to potassium current activation

A. E. Watts, J. T. Williams, G. Henderson

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Abstract

1. The properties of the hyperpolarization-activated cation current (I(h)), and its modulation by γ-aminobuturic acid-B (GABA(B)) receptor activation and protein kinase A, were investigated using whole cell voltage clamp of substantia nigra zona compacta principal neurons in rat midbrain slices in vitro. 2. At 30°C, I(h) activated between -75 and -155 mV, with a V(1/2) of -115 mV. At 35°C, the activation curve shifted positive by 10 mV. I(h) had an estimated reversal potential of -27 mV. Ion substitution experiments showed that the current was carried by Na+ and K+. 3. Application of the GABA(B) receptor agonist baclofen (30 μM) induced an outward potassium current (G(IRK)), increased neuronal membrane conductance and inhibited I(h). The inhibition of I(h) was voltage independent. Baclofen induced an 11-mV positive shift in the reversal potential of I(h). 4. Extracellular barium (300 μM) markedly reduced the baclofen-evoked outward current and associated 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 increase in membrane conductance due to G(IRK) activation and the inhibition of I(h) evoked by baclofen were reduced by a similar extent. 5. Neither forskolin (10 μM) nor the protein kinase A inhibitor, H89 (10 μM), had any effect on I(h) or its inhibition by baclofen. 6. These data suggest that the inhibition of I(h) by baclofen is secondary to the activation of G(IRK), i.e., due directly to alteration of membrane conductance, rather than a distinct effect, and is not mediated by inhibition of adenylyl cyclase.

Original languageEnglish (US)
Pages (from-to)2262-2270
Number of pages9
JournalJournal of neurophysiology
Volume76
Issue number4
DOIs
StatePublished - Oct 1996

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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