title: Stimulation of L-type Ca2+ current in human atrial myocytes by insulin.
abstract: OBJECTIVE
  The L-type calcium current (ICa,L) in isolated human atrial myocytes was investigated as a possible target of insulin in the regulation of cardiac function.
  
  
  METHODS
  Atrial myocytes were obtained from patients undergoing cardiac surgery. Using the whole-cell configuration of the patch-clamp technique, we investigated the stimulation of ICa,L by insulin in single human atrial myocytes.
  
  
  RESULTS
  We found a dose-dependent stimulation of ICa,L by insulin at concentrations of 100 nM, 1 microM and 10 microM. Maximum stimulation of ICa,L over basal ICa,L was 140 +/- 12% (n = 11) at 10 microM insulin. The maximum conductance of ICa,L was increased by 10 microM insulin from 4.0 +/- 0.3 nS to 8.3 +/- 1.0 nS (n = 6). The stimulation of ICa,L by insulin was dose-dependent and reversible. Isoproterenol (10 nM) that stimulates ICa,L by 271 +/- 48% (n = 10) over basal ICa,L acted faster than insulin. The half-maximum stimulation of ICa,L by isoproterenol and insulin (10 microM) was reached after 31 +/- 2 s and 52 +/- 5 s, respectively. The insulin effect shown was totally reversed by acetylcholine (3 microM) which is known to inhibit adenylyl cyclase activity/cAMP-production via Gi-proteins. Also, the selective insulin receptor tyrosine kinase inhibitor (hydroxy-2-naphthanelyl-methyl)phosphonic acid completely inhibited the insulin induced effect.
  
  
  CONCLUSIONS
  Our data show that insulin stimulates the L-type calcium current in isolated human atrial myocytes in a dose-dependent and reversible manner which appears to involve the insulin receptor tyrosine kinase. Insulin regulation of ICa,L in human atrial myocytes may be an interesting system for the analysis of the metabolic syndrome in man.
authors.affiliation: Medizinische Universitätsklinik Würzburg, Germany. s.maier@medizin.uni-wuerzburg.de
authors.forename: S
authors.initials: S
authors.lastname: Maier
authors.forename: F
authors.initials: F
authors.lastname: Aulbach
authors.forename: A
authors.initials: A
authors.lastname: Simm
authors.forename: V
authors.initials: V
authors.lastname: Lange
authors.forename: H
authors.initials: H
authors.lastname: Langenfeld
authors.forename: H
authors.initials: H
authors.lastname: Behre
authors.forename: U
authors.initials: U
authors.lastname: Kersting
authors.forename: U
authors.initials: U
authors.lastname: Walter
authors.forename: M
authors.initials: M
authors.lastname: Kirstein
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002478:Cells, Cultured; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D006325:Heart Atria; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D063065:Organophosphonates / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011972:Receptor, Insulin / Q000037:antagonists & inhibitors; D013268:Stimulation, Chemical; D013997:Time Factors
chemical_list: D020746:Calcium Channels, L-Type; D007328:Insulin; D063065:Organophosphonates; D011972:Receptor, Insulin; D007545:Isoproterenol; D000109:Acetylcholine