Action potential afterdepolarization mediated by a Ca2+-activated cation conductance in myenteric AH neurons
| Autor: | Fivos Vogalis, John B. Furness, Rink-Jan Lohman, John R. Harvey |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Patch-Clamp Techniques
Charybdotoxin Stereochemistry Guinea Pigs Action Potentials Cesium Myenteric Plexus Gluconates Afterdepolarization chemistry.chemical_compound Chlorides medicine Animals Cyclooxygenase Inhibitors Patch clamp Reversal potential HEPES Voltage-dependent calcium channel Chemistry Ryanodine receptor General Neuroscience Niflumic acid Electric Conductivity Niflumic Acid Immunohistochemistry Potassium Biophysics Calcium Calcium Channels medicine.drug |
| Zdroj: | Neuroscience. 115:375-393 |
| ISSN: | 0306-4522 |
| Popis: | We investigated the nature of afterdepolarizing potentials in AH neurons from the guinea-pig duodenum using whole-cell patch-clamp recordings in intact myenteric ganglia. Afterdepolarizing potentials were minimally activated following action-potential firing under normal conditions, but after application of charybdotoxin (40 nM) or tetraethyl ammonium (TEA; 10-20 mM) to the bathing solution, prominent afterdepolarizing potentials followed action potentials. The whole-cell current underlying afterdepolarizing potentials (I(ADP)) in the presence of TEA (10-20 mM) reversed at -38 mV and was not voltage-dependent. Reduction of NaCl in the bathing (Krebs) solution to 58 mM shifted the reversal potential of the I(ADP) to -58 mV, suggesting that the current underlying the afterdepolarizing potential was carried by a mixture of cations. The relative contributions of Na(+) and K(+) to this current were estimated to be about 1:5. Substitution of external Na(+) with N-methyl D-glucamine blocked the current while replacement of internal Cl(-) with gluconate did not block the I(ADP). The I(ADP) was also inhibited when CsCl-filled patch pipettes were used. The I(ADP) was blocked or substantially decreased in amplitude in the presence of N-type Ca(2+) channel antagonists, omega-conotoxin GVIA and omega-conotoxin MVIIC, respectively, and was eliminated by external Cd(2+), indicating that it was dependent on Ca(2+) entry. The I(ADP) was also inhibited by ryanodine (10-20 microM), indicating that Ca(2+)-induced Ca(2+) release was involved in its activation. Niflumic acid consistently inhibited the I(ADP) with an IC(50) of 63 microM. Using antibodies against the pore-forming subunits of L-, N- and P/Q-type voltage-gated Ca(2+) channels, we have demonstrated that myenteric AH neurons express N- and P/Q, but not L-type voltage-gated Ca(2+) channels. We conclude that the ADP in myenteric AH neurons, in the presence of an L-type Ca(2+)-channel blocker, is generated by the opening of Ca(2+)-activated non-selective cation channels following action potential-mediated Ca(2+) entry mainly through N-type Ca(2+) channels. Ca(2+) release from ryanodine-sensitive stores triggered by Ca(2+) entry contributes significantly to the activation of this current. |
| Databáze: | OpenAIRE |
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