Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Jeck, C. et al.

Transient outward currents in subendocardial Purkinje myocytes surviving in the infarcted heart.

BACKGROUND: Altered electrical activity of subendocardial Purkinje fibers contributes to arrhythmias in the 48-hour infarcted canine heart. Changes in the transmembrane action potentials of these fibers include marked action potential prolongation. The ionic basis for these changes is unknown. METHODS AND RESULTS: We used whole-cell voltage-clamp techniques to study 4-aminopyridine (4-AP)-sensitive voltage-dependent transient outward currents (Ito1) in Purkinje myocytes isolated from LV subendocardial (n = 14) and free-running (n = 15) bundles of the normal canine heart. Ito1 in these two groups of control cells (normal-zone Purkinje cells [NZPCS]) did not differ. NZPCS Ito1 was then compared with Ito1 of Purkinje myocytes dispersed from subendocardium of infarcted hearts 48 hours after total coronary artery occlusion (IZPC48, n = 14). Ito1 amplitude and current density were significantly reduced (P < .01) in IZPC48s (1650 +/- 389 pA, 9 +/- 2 pA/pF) compared with NZPCS (2917 +/- 267 pA, 20.2 +/- 2 pA/pF) at Vt = +55 mV, Vh = -60 mV, where Vt is test potential and Vh is holding potential. Decay of Ito1 was biexponential in all NZPCS but monoexponential in 71% of IZPC48s. Both NZPCS and IZPC48s have a sustained 4-AP-sensitive component (at 250 ms, Vt = +55 mV: 4 +/- 1 pA/pF, 3 +/- 1 pA/pF, respectively). Ito1 voltage dependence of inactivation did not differ between groups. In IZPC48s, recovery of Ito1 from inactivation was slowed significantly. Furthermore, significantly more Ito1 was seen with rapid pacing in NZPCS (cycle length [CL] 5000 ms = 100%, CL 1300 ms = 73%, CL 330 ms = 46%) than in IZPC48s (CL 5000 ms = 100%, CL 1300 ms = 58%, CL 330 ms = 31%). In three IZPC48s, no Ito1 was seen at CL 330 ms. CONCLUSIONS: Ito1 plays a major role in normal Purkinje myocyte electrophysiology, contributing both a large transient and a sustained component that are 4-AP-sensitive. In subendocardial Purkinje myocytes that survive in the 48-hour infarcted heart, density of Ito1 is markedly reduced and the remaining Ito1 showed specific changes in kinetics. The alterations observed in both Ito1 density and function could contribute to abnormally long transmembrane action potentials of these arrhythmogenic Purkinje myocytes of the infarcted heart.[1]

References

Transient outward currents in subendocardial Purkinje myocytes surviving in the infarcted heart. Jeck, C., Pinto, J., Boyden, P. Circulation (1995) [Pubmed]

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