Phorbol ester‐induced M‐current suppression in bull‐frog sympathetic ganglion cells: insensitivity to kinase inhibitors

• Published in: British journal of pharmacology Vol. 113; no. 1; pp. 55 - 62
• Main Authors: Chen, Hsinyo, Jassar, Balvinder S., Kurenny, Dmitry E., Smith, Peter A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.1994; Nature Publishing
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Animals; autonomic ganglia; Biological and medical sciences; Diglycerides - pharmacology; Fundamental and applied biological sciences. Psychology; Ganglia, Sympathetic - cytology; Ganglia, Sympathetic - drug effects; Ganglia, Sympathetic - metabolism; G‐protein; Isoquinolines - pharmacology; Muscarinic Agonists - pharmacology; muscarinic receptor; M‐current; Neurons - drug effects; Neurons - metabolism; Patch-Clamp Techniques; Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ; phorbol ester; Phorbol Esters - pharmacology; Phorbols - pharmacology; Piperazines - pharmacology; Potassium channel; protein kinase; Protein Kinase C - antagonists & inhibitors; Protein Kinase Inhibitors; Rana catesbeiana; Receptors, Muscarinic - drug effects; Tetradecanoylphorbol Acetate - pharmacology; Vertebrates: nervous system and sense organs; Enzyme; Frog; Transferases; Amphibia; Electrophysiology; Enzyme inhibitor; Salientia; Ionic channel; Ionic current; Nervous ganglion; Vertebrata; Autonomic nervous system; Protein kinase; Muscarinic receptor; Potassium; G protein
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1994.tb16173.x

1 The effects of 1‐oleoyl‐2‐acetyl‐sn‐glycerol (OAG), phorbol 12‐myristate 13‐acetate (PMA), 4‐α‐phorbol and muscarine on B‐neurones from bull‐frog sympathetic ganglion were studied by means of whole‐cell patch‐clamp recording. With the exception of 4‐α‐phorbol, all of these agonists reduced the steady‐state outward current recorded at −30 mV as a result of suppression of a voltage‐dependent, non‐inactivating K+‐current, the M‐current, (IM). 2 Of the cells tested, 34% displayed bona fide responses to OAG (20 μm). The chance of recording a response was not decreased when the protein kinase inhibitor, 1‐(5‐isoquinolinylsulphonyl)‐2‐methyl‐piperazine (H‐7; 50 or 75 μm) was included simultaneously in the extracellular solution and in the pipette solution. 3 The presence of 50 μm H‐7 on both sides of the membrane or 500 nm staurosporine in the pipette solution did not prevent responses to brief (1–2 min) or prolonged (>20 min) applications of PMA. 4 Brief (1–2 min) extracellular application of H‐7 (300 μm) suppressed IM by about 29%. 5 The most likely explanation of these data is that PMA and OAG modulate IM via a mechanism that is independent of protein kinase C (PKC). The availability of such a mechanism poses new questions as to the mechanism of muscarine‐induced IM suppression.