Equal changes in L-type calcium channel density after 60 min of ischaemia in normal and ischaemically preconditioned porcine myocardium.
Long-lasting myocardial ischaemia reduces the density of sarcolemmal L-type calcium channels (LCC). Ischaemic preconditioning protects the myocardium against development of infarction. The aim of this study was to investigate if ischaemia-induced loss in LCC is affected by ischaemic preconditioning. Specific (+) - [3H]isradipine binding to LCC was compared in membranes and homogenates from control and ischaemic regions of non-preconditioned and ischaemically preconditioned hearts [two 10 min left anterior descending coronary artery (LAD) occlusions, each followed by 30 min reperfusion]. Biopsies were sampled after 60 min mid LAD occlusion from ischaemic and control (supplied by circumflex artery) regions. Sixty min ischaemia reduced binding density of specific (+) - [3H]isradipine in membranes by 23 +/- 11% (n = 7, P < 0.05) in the non-preconditioned group and by 20 +/- 8% (n = 6, P < 0.05) in the preconditioned group. Binding density in homogenates was reduced by 36 +/- 5% (n = 5. P < 0.05) in the non-preconditioned group and by 21 +/- 5% (n = 5. P < 0.05) in the preconditioned group. The reductions in the two groups and reductions in membranes and homogenates were not statistically different. The dissociation constant of binding was similar in the groups. In conclusion, 60 min of ischaemia reduced the binding density of (+)-[3H]isradipine in membranes and homogenates by 20-36%. The reduction in density of binding sites was not caused by redistribution of sarcolemmal LCC to an intracellular compartment. Ischaemic preconditioning did not affect the decline in binding density as hypothesized.
Stokke
M
M
Clinical Chemistry Department, Ulleval University Hospital, Oslo, Norway.
Kirkebøen
K A
KA
Naess
P A
PA
Hagelin
E M
EM
Ilebekk
A
A
Brørs
O
O
D000818:Animals; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics; D015220:Calcium Channels / Q000378:metabolism*; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D017275:Isradipine / Q000493:pharmacokinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D013552:Swine; D017725:Ventricular Pressure / Q000502:physiology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D017275:Isradipine