© 1996 American Heart Association, Inc.
Articles |
Nitric Oxide Synthase Activity in Guinea Pig Ventricular Myocytes Is Not Involved in Muscarinic Inhibition of cAMP-Regulated Ion Channels
From the Departments of Physiology and Biophysics (S.I.Z., S.P., N.R.P., R.D.H.) and Biochemistry (G.K.K.), Case Western Reserve University, Cleveland, Ohio.
Correspondence to Dr Robert Harvey, Department of Physiology and Biophysics, Case Western Reserve University, 2109 Adelbert Rd, Cleveland, OH 44106-4970. E-mail rdh3@po.cwru.edu.
Abstract It has recently been demonstrated that NO plays an obligatory role in muscarinic inhibition of ß-adrenergically stimulated ion channels in cardiac sinoatrial node cells (J Gen Physiol. 1995;106:45-65). We looked for evidence that NO might play a similar role in ventricular cells by using histochemical staining for NO synthase (NOS) activity and whole-cell patch-clamp recording of cAMP-regulated Cl- currents. Myocytes isolated from guinea pig hearts stained positively for NADPH-diaphorase activity, suggesting that these cells do express NOS. Acetylcholine (ACh) inhibition of the R(-)-isoproterenol bitartrate (Iso)–activated Cl- current was also reversed by the cGMP-lowering agents LY-83583 and methylene blue, consistent with the idea that NO activation of guanylate cyclase may contribute to muscarinic responses. However, LY-83583 and methylene blue activated the Cl- current in the presence of subthreshold concentrations of Iso alone, suggesting that their effects may not be due to antagonism of an NO/cGMP-dependent response. Furthermore, ACh inhibition of Iso-activated Cl- currents could not be mimicked by the NO donors sodium nitroprusside, 3-morpholinosydnonimine, and spermine-NO. Similarly, ACh inhibition of the Iso-activated Cl- current could not be blocked by the NOS inhibitor NG-monomethyl-L-arginine. These results indicate that even though ventricular myocytes possess NOS activity, NO production does not play an important role in muscarinic inhibition of ß-adrenergically regulated Cl- channels in these cells.
Key Words: acetylcholine • muscarinic regulation • isoproterenol • ß-adrenergic regulation • nitric oxide donors
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