α‐Conotoxin M1 (CTx) blocks αδ binding sites of adult nicotinic receptors while ACh binding at αε sites elicits only small and short quantal synaptic currents
| Autor: | Josef Dudel |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
mouse nicotinic receptor
Nicotinic Receptors Physiology Chemistry Muscarinic acetylcholine receptor M2 Depolarization Muscarinic acetylcholine receptor M1 CTx block transmission chemistry.chemical_compound Physiology (medical) Mole Methoctramine Biophysics binding site specificity Binding site Receptor presynaptic muscarinic receptors Original Research |
| Zdroj: | Physiological Reports |
| ISSN: | 2051-817X |
| Popis: | In ‘embryonic’ nicotinic receptors, low CTx concentrations are known to block only the αδ binding site, whereas binding of ACh at the αγ‐site elicits short single channel openings and short bursts. In adult muscles the αγ‐ is replaced by the αε‐site. Quantal EPSCs (qEPSCs) were elicited in adult muscles by depolarization pulses and recorded through a perfused macropatch electrode. One to 200 nmol L−1 CTx reduced amplitudes and decay time constants of qEPSCs, but increased their rise times. CTx block at the αδ binding sites was incomplete: The qEPSCs still contained long bursts from not yet blocked receptors, whereas their average decay time constants were reduced by a short burst component generated by ACh binding to the αε‐site. Two nanomolar CTx applied for 3 h reduced the amplitudes of qEPSCs to less than half with a constant slope. The equilibrium concentration of the block is below 1 nmol L−1 and lower than that of embryonic receptors. CTx‐block increased in proportion to CTx concentrations (average rate 2 × 104 s−1·mol−1 L). Thus, the reactions of ‘embryonic’ and of adult nicotinic receptors to block by CTx are qualitatively the same. – The study of the effects of higher CTx concentrations or of longer periods of application of CTx was limited by presynaptic effects of CTx. Even low CTx concentrations severely reduced the release of quanta by activating presynaptic M2 receptors at a maximal rate of 6 × 105 s−1·mol−1 L. When this dominant inhibition was prevented by blocking the M2 receptors with methoctramine, activation of M1 receptors was unmasked and facilitated release. When CTx blocks the αδ binding site of adult nicotinic receptors, very small and short quantal synaptic currents (qEPSCs) are generated by binding of ACh quanta at the αε‐site, This is very similar to the effects of CTx at embryonic receptors where the short qEPSCs are generated by binding at the αγ site. CTx also activates presynaptic muscarinic M1 and M2 receptors. |
| Databáze: | OpenAIRE |
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