Cholesterol increases the L-type voltage-sensitive calcium channel current in arterial smooth muscle cells.
To determine whether membrane free cholesterol affects calcium currents in vascular smooth muscle cells, whole-cell patch clamp recordings were made before and after cholesterol enrichment of cells by exposure to cholesterol-rich liposomes. Exposure to cholesterol-rich liposomes resulted in a gradual increase in the L-type current over 20 hours and a plateau (73 +/- 7% increase over basal) between 20 and 32 hours. This effect was associated with a rightward shift in the inactivation potential and a decrease in the sensitivity to (-)-PN-202-791, a dihydropyridine antagonist. There was no change in the maximum L-type current stimulated by (+)-PN-202-791, a dihydropyridine agonist. Liposome exposure caused a small, transient increase in the T-type current (peak effect, 20 minutes). We conclude that membrane cholesterol has important effects on the L-type calcium current in vascular smooth muscle cells, which is most likely due to an alteration in channel functional state rather than an increase in channel expression.
Sen
L
L
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Bialecki
R A
RA
Smith
E
E
Smith
T W
TW
Colucci
W S
WS
D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002460:Cell Line; D002784:Cholesterol / Q000502:physiology*; D004095:Dihydropyridines / Q000037:antagonists & inhibitors; D008081:Liposomes; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D009539:Nicotinic Acids / Q000494:pharmacology; D010069:Oxadiazoles; D011651:Pulmonary Artery; D051381:Rats; D013997:Time Factors
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D008081:Liposomes; D009539:Nicotinic Acids; D010069:Oxadiazoles; C049834:PN 202-791; D002784:Cholesterol