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Neurotensin Inhibition of the Hyperpolarization‐Activated Cation Current ( I h ) in the Rat Substantia Nigra Pars Compacta Implicates the Protein Kinase C Pathway
Author(s) -
Cathala L.,
PaupardinTritsch D.
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1997.087bi.x
Subject(s) - forskolin , chemistry , protein kinase c , substantia nigra , endocrinology , chelerythrine , reversal potential , diacylglycerol kinase , medicine , pars compacta , biophysics , patch clamp , biochemistry , biology , signal transduction , dopamine , receptor , dopaminergic
1 Whole‐cell patch‐clamp recording was performed from principal neurones of the substantia nigra pars compacta (SNc). In 66% of these neurones, neurotensin (NT) induced, at −60 mV, an inward current associated with an increase in conductance. 2 Principal neurones displayed, in response to hyperpolarizing voltage steps, the voltage‐dependent inward cationic current, I h . This current activated at potentials more negative than −65 mV and reached a maximum at −106 ± 4 mV, with a half‐activation potential of −86 ± 3 mV. Its estimated reversal potential was −43 ± 7 mV and its activation curve was fitted with two exponentials. 3 In 41 % of neurones showing the inward current, NT (0.5 μM) also reversibly reduced the amplitude of I h . The diminution was 48.5 ± 12% when voltage steps were made from −60 to −95 mV. The decrease in I h resulted from a reduction in the maximal current with no change in the voltage dependence of activation. 4 Forskolin (10 μM), an activator of adenylate cyclase, increased I h by shifting its activation range to more positive potentials, but it did not alter the NT inhibition of I h . 5 The effect of NT was blocked by staurosporine (0.5 μM) and by PKC‐(19–31) (0.5 μM), a specific protein kinase C (PKC) inhibitor, but was unaffected by Walsh's peptide (100 μM), a specific inhibitor of protein kinase A. The reduction of I h was mimicked by 1‐oleoyl‐2‐acetyl‐ sn ‐glycerol (0.5–10 μM), an analogue of diacylglycerol, an endogenous PKC activator. 6 These results suggest that the inhibition of I h by NT involves a phosphorylation mechanism that implies activation of PKC.