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Cholesterol regulates β‐adrenergic enhancement of L‐type Ca current in rat ventricular myocytes
Author(s) -
Ochi Rikuo,
Tsujikawa Hiroto,
Okada Takao,
Wolin Michael S,
Gupte Sachin A
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1201.2
Subject(s) - chemistry , endocrinology , medicine , myocyte , caveolae , extracellular , cholesterol , lipid raft , receptor , biophysics , membrane , biology , biochemistry
Cholesterol is a primary constituent of the plasma membrane, including lipid rafts/caveolae where various G protein‐coupled receptors colocalize with signaling proteins and channels. We studied roles of cholesterol in the β‐adrenergic modulatinon of L‐type Ca 2+ currents ( I Ca,L ) in rat ventricular myocytes using methyl‐β‐cyclodextrin (CD) and its cholesterol‐saturated complex (CD:chol). Exposing the myocytes to 10 mM‐CD for 10 min decreased cellular cholesterol content by 50%, while that to 5 mM CD:chol increased it by 40%. Isoproterenol (ISO) increased I Ca,L 2.6‐fold and caused a negative shift in V 0.5 . Extracellular application of 10 mM‐CD for 10 min depressed the ISO‐induced I Ca,L increase to 1.9‐fold and dialysis of 30 mM‐CD from pipette solution for 10 min suppressed the increase to 1.2‐fold. This dialysis‐induced suppression was recovered to 1.8‐fold by simultaneous superfusion of 15 mM CD:chol. However, dialysis of 30 mM CD:chol alone depressed significantly the ISO‐induced I Ca,L increase to 1.7‐fold. These result suggest that normal density of cholesterol in the membrane is optimal for the β‐adrenergic increase in I Ca,L . Cholsterol may regulate structural coupling of L‐type Ca 2+ channels and adjacent regulatory proteins.