| 12649591 |
Shi H, Yang B, Xu D, Wang H, Wang Z: Electrophysiological characterization of cardiac muscarinic acetylcholine receptors: different subtypes mediate different potassium currents. Cell Physiol Biochem. 2003;13(2):59-74.
To characterize electrophysiologically the K+ currents mediated by various mAChR subtypes, we performed detailed whole-cell patch-clamp studies in canine atrial myocytes. I (KACh) was induced by 1 mM ACh (acetylcholine) or by arecaidine but-2-ynyl ester tosylate (100 nM, an M2 receptor selective agonist) and was blocked by methoctramine (20 nM, an M2 receptor selective antagonist). Tetramethylammonium (0.5 mM) activated a K+ conductance with delayed rectifying properties (I (KM3)) and the currents were highly sensitive to 4-diphenylacetoxy-N-methylpiperidine methiodide (2 nM, an M3 receptor inhibitor). 4-aminopyridine (1 mM) induced a delayed rectifier-like current (I (K4AP)) which was selectively suppressed by tropicamide (200 nM, an M4 receptor blocker). The current waveforms, I-V relationships, steady-state voltage-dependence, kinetics and pharmacological properties of these three currents were different from one another and distinct from the classical delayed rectifier K+ currents (I (Kr) and I (Ks)). Both I (KACh) and I (K4AP) were sensitive to pertussis ntoxin, whereas I (KM3) was not. Isoproterenol (1 mM) markedly depressed I (KM3), but increased I (K4AP) and did not alter I (KACh). The effects of isoproterenol were reversed by propranolol (1 mM); and ACh completely suppressed I (KM3) and I (K4AP). The results suggest that the K+ currents mediated by different subtypes of mAChR represent different populations of K+ channels and that the cholinergic regulation of the heart's electrical function is a consequence of activating multiple mAChRs linked to different effector systems with potentially varying signal transduction. |
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