![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 55, Issue 3, 497-507, March 1999
Department of Medicine, University of Montreal, Montreal, Quebec,
Canada (Z.W.), and
Research Center, Montreal Heart Institute, Montreal,
Quebec, Canada (H.S., H.W., Z.W.)
M2 receptors have long been believed to be the only
functional subtype of muscarinic acetylcholine receptor (mAChR) in the heart, although recent studies have provided evidence for the presence
of other subtypes. We performed a detailed study to clarify this issue.
In the presence of tetramethylammonium (1 µM to 10 mM), a novel
K+ current with both delayed rectifying and inward
rectifying properties (IKTMA) was activated in single
canine atrial myocytes. 4-Aminopyridine (0.05-2 mM) also induced a
K+ current (IK4AP) with characteristics similar
to but distinct from those of IKTMA. Both IKTMA
and IK4AP were abolished by 1 µM atropine.
IK4AP, but not IKTMA, was minimized by
treatment with pertussis toxin. IKTMA was markedly
decreased by 4-diphenylacetoxy-N-methylpiperidine methiodide (a selective antagonist for M3 subtype) but was
not altered by pirenzepine (for M1), methoctramine (for
M2), and tropicamide (for M4). Tropicamide
substantially reduced IK4AP, but the antagonists for other
mAChR subtypes had no effects on IK4AP. By comparison, IKACh (ACh-induced K+ current) was
significantly depressed by methoctramine but was unaltered by other
antagonists. Results from displacement binding of
[methyl-3H]N-scopolamine
methyl chloride with pirenzepine, methoctramine, 4-diphenylacetoxy-N-methylpiperidine methiodide, or
tropicamide revealed the coexistence of multiple mAChR subtypes in
canine atrium. Cloning of cDNA fragments and detection of mRNAs coding for M2, M3, and M4 provided further
supporting evidence. Our results suggest that 1) multiple subtypes of
mAChRs (M2/M3/M4) coexist in the
dog heart and 2) different subtypes of mAChRs are coupled to different
K+ channels. Our findings represent the first functional
evidence for the physiological role of cardiac M3 and
M4 receptors.
This article has been cited by other articles:
|
|
 |
|
  H. Shi, H. Wang, B. Yang, D. Xu, and Z. Wang The M3 Receptor-mediated K+ Current (IKM3), a Gq Protein-coupled K+ Channel J. Biol. Chem., May 21, 2004; 279(21): 21774 - 21778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wang, H. Wang, Y. Zhang, H. Gao, S. Nattel, and Z. Wang Impairment of HERG K+ Channel Function by Tumor Necrosis Factor-{alpha}: ROLE OF REACTIVE OXYGEN SPECIES AS A MEDIATOR J. Biol. Chem., April 2, 2004; 279(14): 13289 - 13292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Han, L. Zhang, G. Schram, and S. Nattel Properties of potassium currents in Purkinje cells of failing human hearts Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2495 - H2503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Sugiyama, G. A. Churchill, R. Li, L. J. M. Libby, T. Carver, K.-I. Yagami, S. W. M. John, and B. Paigen QTL associated with blood pressure, heart rate, and heart weight in CBA/CaJ and BALB/cJ mice Physiol Genomics, July 12, 2002; 10(1): 5 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Krejci and S. Tucek Quantitation of mRNAs for M1 to M5 Subtypes of Muscarinic Receptors in Rat Heart and Brain Cortex Mol. Pharmacol., June 1, 2002; 61(6): 1267 - 1272. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Hardouin, K. N. Richmond, A. Zimmerman, S. E. Hamilton, E. O. Feigl, and N. M. Nathanson Altered Cardiovascular Responses in Mice Lacking the M1 Muscarinic Acetylcholine Receptor J. Pharmacol. Exp. Ther., April 1, 2002; 301(1): 129 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wang, H. Han, L. Zhang, H. Shi, G. Schram, S. Nattel, and Z. Wang Expression of Multiple Subtypes of Muscarinic Receptors and Cellular Distribution in the Human Heart Mol. Pharmacol., April 16, 2001; 59(5): 1029 - 1036. [Abstract] [Full Text]
|
|
|
|
 |
|
 V. Oberhauser, E. Schwertfeger, T. Rutz, F. Beyersdorf, and L. C. Rump Acetylcholine Release in Human Heart Atrium : Influence of Muscarinic Autoreceptors, Diabetes, and Age Circulation, March 27, 2001; 103(12): 1638 - 1643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Han, Z. Wang, and S. Nattel Slow delayed rectifier current and repolarization in canine cardiac Purkinje cells Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H1075 - H1080. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wang, H. Shi, L. Zhang, M. Pourrier, B. Yang, S. Nattel, and Z. Wang Nicotine Is a Potent Blocker of the Cardiac A-Type K+ Channels : Effects on Cloned Kv4.3 Channels and Native Transient Outward Current Circulation, September 5, 2000; 102(10): 1165 - 1171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W. Stengel, J. Gomeza, J. Wess, and M. L. Cohen M2 and M4 Receptor Knockout Mice: Muscarinic Receptor Function in Cardiac and Smooth Muscle In Vitro J. Pharmacol. Exp. Ther., March 1, 2000; 292(3): 877 - 885. [Abstract] [Full Text]
|
|
|
|
|
|
H. Shi, H.-Z. Wang, and Z. Wang Extracellular Ba2+ blocks the cardiac transient outward K+ current Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H295 - H299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O.-E. Brodde and M. C. Michel Adrenergic and Muscarinic Receptors in the Human Heart Pharmacol. Rev., December 1, 1999; 51(4): 651 - 690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. W. Stengel, M. Yamada, J. Wess, and M. L. Cohen M3-receptor knockout mice: muscarinic receptor function in atria, stomach fundus, urinary bladder, and trachea Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2002; 282(5): R1443 - R1449. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
