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Melanostatin (NPY) inhibited electrical activity in frog melanotrophs through modulation of K+, Na+ and Ca2+ currents.
Author(s) -
Valentijn J A,
Vaudry H,
Kloas W,
Cazin L
Publication year - 1994
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 - 10.1113/jphysiol.1994.sp020060
Subject(s) - vasoactive intestinal peptide , voltage clamp , hyperpolarization (physics) , medicine , chemistry , endocrinology , biophysics , reversal potential , membrane potential , gtp' , patch clamp , electrophysiology , neuropeptide , biology , biochemistry , stereochemistry , receptor , nuclear magnetic resonance spectroscopy , enzyme
1. Melanostatin, a thirty‐six amino acid peptide recently isolated from the frog brain due to its ability to inhibit alpha‐melanocyte‐stimulating hormone (alpha‐MSH) release, is the amphibian counterpart of mammalian neuropeptide Y (NPY). The effect of synthetic melanostatin on the bioelectrical activity of cultured frog melanotrophs was studied in 124 cells by using the whole‐cell patch‐clamp technique. 2. In current‐clamp experiments, melanostatin (1 microM) provoked a reversible hyperpolarization and a suppression of spontaneous action potentials. In some cells the hyperpolarizing response was absent, but an arrest of spike firing still occurred. 3. Melanostatin‐induced hyperpolarization was associated with a decrease in membrane resistance. In voltage‐clamp experiments, melanostatin induced an outward current at a constant command potential. This hyperpolarizing outward current appeared to be carried by potassium ions. 4. Cell dialysis with the non‐hydrolysable GTP analogue guanosine‐5'‐O‐(3‐thiotriphosphate) (GTP gamma S) sustained the outward current produced by melanostatin. Dopamine (1 microM), which generates a similar hyperpolarizing outward current in frog melanotrophs, was not capable of increasing the current provoked by melanostatin and sustained by GTP gamma S. 5. Melanostatin also modulated voltage‐operated currents. The amplitude of voltage‐activated potassium current was increased by 30%. 6. Melanostatin reduced the fast sodium current. This inhibitory effect was rather persistent compared to the other modulated currents. 7. Melanostatin markedly scaled down high voltage‐activated N‐ and L‐like calcium currents. The activation kinetics of these two calcium currents were not altered by the peptide. 8. Pretreatment of melanotrophs with pertussis toxin (1 microgram ml‐1) blocked melanostatin‐induced inhibition of N‐ and L‐like calcium currents. 9. It is concluded that the NPY‐related peptide melanostatin generates a very complex pattern of electrical responses in frog melanotrophs, including hyperpolarization and modulation of voltage‐activated currents underlying action potentials. G proteins appear to mediate at least part of these effects.