Altered Pharmacologic Responsiveness of Reduced L‐Type Calcium Currents in Myocytes Surviving in the Infarcted Heart

摘要: Altered Pharmacology of Ica,L in Myocytes From Infarcted Heart. The pharmacologic responses macroscopic L-type calcium channel currents to the dihydropyridine agonist, Bay K 8644, and β-adrenergic receptor stimulation by isoproterenol were studied myocytes enzymatically dissociated from epicardial border zone arrhythmic 5-day infarcted canine heart (IZs). Calcium recorded at 36° 37° C using whole cell, patch clamp method elicited applying step depolarizations a holding potential -40 mV various test potentials for 250-msec duration 8-second intervals. A Cs+ -rich 10 mM EGTA-containing pipette solution Na+-and K+-free external solutions used isolate other contaminating currents. During control, peak Ica,L, density was found be significantly less IZs (4.0 ± 1.1 pA/pF) than dispersed epicardium normal noninfarcted (NZs; 6.5 1.8 pA/pF). 8644 (I μM) increased 3.5-fold above control levels both NZs (to 22.5 6.2 pA/pF; n = 7) 12.8 3.0 5), yet presence drug NZs. effects on kinetics current decay steady-state inactivation relations similar two cell types. In contrast, response (1 diminished compared regardless whether Ba2+ or Ca2+ ions carried current. Thus, these results indicate an altered responsiveness cells that survive heart. Furthermore, application forskolin μM intracellular cAMP (200 μM), agents known act downstream β-receptor, also produced smaller increase IBa versus NZs, suggesting multiple defects exist signaling pathway IZs. conclusion, studies illustrate reduced infracted exhibit profile has important implications development drugs diseased