CHARACTERIZATION OF INWARDLY RECTIFYING K- ALTERATIONS IN CHANNEL BEHAVIOR IN MYOCYTES ISOLATED FROM PATIENTS WITH IDIOPATHIC DILATED CARDIOMYOPATHY( CHANNEL IN HUMAN CARDIAC MYOCYTES )

Background Little is known about the characteristics of the inwardly r ectifying K+ channel (I-K1) and the influence of preexisting heart dis ease on the channel properties in the human heart. Methods and Results We studied the characteristics of cardiac I-K1 in freshly isolated ad ult human atrial and ventricular myocytes by using the patch-clamp tec hnique. Specimens were obtained from the atria and ventricles of 48 pa tients undergoing cardiac surgery or transplantation and from four exp lanted donor hearts. The action potential in ventricular myocytes exhi bited a longer duration (391.4+/-30.2 milliseconds at 90% repolarizati on, n=10) than in atrium (289.4+/-23.0 milliseconds, n=18, P<.001) and had a fast late repolarization phase (phase 3). The final phase of re polarization in ventricle was frequency independent. Whole-cell I-K1 i n ventricle exhibited greater slope conductance (84.0+/-7.9 nS at the reversal potential, E(K); n=27) than in atrium (9.7+/-1.2 nS at E(K); n=8, P<.001). The steady-state current-voltage (I-V) relation in Ventr icular I-K1 demonstrated inward rectification with a region of negativ e slope. This negative slope region was not prominent in atrial I-K1. The macroscopic currents were blocked by Ba2+ and Cs+. The channel cha racteristics in ventricular myocytes from patients with congestive hea rt failure after idiopathic dilated cardiomyopathy (DCM) exhibited dis tinct properties compared with those from patients with ischemic cardi omyopathy (ICM). The action potential in ventricular myocytes from pat ients with DCM had a longer duration (490.8+/-24.5 milliseconds, n=11) compared with that for ICM (420.6+/-29.6 milliseconds, n=11, P<.01) a nd had a slow repolarization phase (phase 3) with a low resting membra ne potential. The whole-cell current slope conductance for DCM was sma ller (41.2+/-9.0 nS at E(K), n=7) than that for ICM (80.7+/-17.0 nS, n =6, P<.05). In single-channel recordings from cell-attached patches, v entricular I-K1 channels had characteristics similar to those of atria l I-K1; channel openings occurred in long-lasting bursts with similar conductance and gating kinetics. In contrast, the percent of patches i n which I-K1 channels were found was 34.7% (25 of 72) of patches in at rium and 88.6% (31 of 35) of patches in ventricle. Single I-K1 channel activity for DCM exhibited frequent long-lasting bursts separated by brief interburst intervals at every holding voltage with the open prob ability displaying little voltage sensitivity (approximate to 0.6). Ch annel activity was observed in 56.2% (18 of 32) of patches for DCM and 77.4% (24 of 31) of patches for ICM. Similar results were obtained fr om atrial I-K1 channels for DCM. In addition, channel characteristics were not significantly different between ICM and explanted donor heart s (donors). I-K1 channels in cat and guinea pig had characteristics vi rtually similar to those of humans, with the exception of lower open p robability than that in humans. Conclusions These results suggest that the electrophysiological characteristics of human atrial and ventricu lar I-K1 channels were similar to those of other mammalian hearts, wit h the possible exception that the channel open probability in humans m ay be higher, that the whole-cell I-K1 density is higher in human vent ricle than in atrium, and that I-K1 channels in patients with DCM exhi bited electrophysiological properties distinct from I-K1 channels foun d in patients with ICM and in donors.