HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 294/5/H2257    most recent 01335.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Chen, X. Articles by Houser, S. R. PubMed PubMed Citation Articles by Chen, X. Articles by Houser, S. R.

Reduced effects of BAY K 8644 on L-type Ca²⁺ current in failing human cardiac myocytes are related to abnormal adrenergic regulation

¹Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania; ²Duke University School of Medicine, Department of Medicine, Durham, North Carolina; ³Cardiovascular Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania

Submitted 13 November 2007 ; accepted in final form 17 March 2008

Abnormal L-type Ca²⁺ channel (LTCC, also named Cav1.2) density and regulation are important contributors to depressed contractility in failing hearts. The LTCC agonist BAY K 8644 (BAY K) has reduced inotropic effects on failing myocardium. We hypothesized that BAY K effects on the LTCC current (I_CaL) in failing myocytes would be reduced because of increased basal activity. Since support of the failing heart with a left ventricular assist device (LVAD) improves contractility and adrenergic responses, we further hypothesized that BAY K effects on I_CaL would be restored in LVAD-supported failing hearts. We tested our hypotheses in human ventricular myocytes (HVMs) isolated from nonfailing (NF), failing (F), and LVAD-supported failing hearts. We found that 1) BAY K had smaller effects on I_CaL in F HVMs compared with NF HVMs; 2) BAY K had diminished effects on I_CaL in NF HVM pretreated with isoproterenol (Iso) or dibutyryl cyclic AMP (DBcAMP); 3) BAY K effects on I_CaL in F HVMs pretreated with acetylcholine (ACh) were normalized; 4) Iso had no effect on NF HVMs pretreated with BAY K; 5) BAY K effects on I_CaL in LVAD HVMs were similar to those in NF HVMs; 6) BAY K effects were reduced in LVAD HVMs pretreated with Iso or DBcAMP; 7) Iso had no effect on I_CaL in LVAD HVMs pretreated with BAY K. Collectively, these results suggest that the decreased BAY K effects on LTCC in F HVMs are caused by increased basal channel activity, which should contribute to abnormal contractility reserve.

heart failure; L-type calcium channel; left ventricular assist device