Key result
Low-dose 4-AP preferentially inhibits human atrial non-inactivating outward K+ currents by ~80%.
Why the study?
Difficulties in harvesting and isolating human cardiac tissue have limited studies on the electrophysiological characteristics of human atrial myocytes.
Human atrial K+ currents can now be recorded directly; extends animal data but leaves open clinical translation.
Background: The cardiac electrophysiological characteristics differ significantly among mammalian species or among various disease processes. However, difficulties in the procedures for harvesting and isolating tissue have precluded studies using human cardiac specimens. Methods: The outward K + -currents were recorded in human atrial myocytes isolated from patients undergoing open heart surgery. The electrophysiological characteristics of the voltage-dependent outward currents were investigated using a whole-cell patchclamp technique. Results: Using depolarizing step pulses, the transient outward currents were activated within 10 msec, which slowly inactivated thereafter. After inactivation, the sustained components of the outward currents remained for up to 5.0 seconds of depolarizing step pulses. While the inactivating component was almost completely inactivated at potentials >+30 mV, the non-inactivating component showed only 10-15% inactivation. The non-inactivating component was highly sensitive to 4-AP and was inhibited by >80% at a concentration of 0.2 mM, while the inactivating component was inhibited by only 25%. The delayed rectifier potassium currents were not recorded. The ratios of the amplitudes of the inactivating and non-inactivating components varied. Conclusions: Two components of the voltage dependent outward K + currents in human cardiac tissue were identified, which could
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Nam et al. (2004) studied Patients undergoing open heart surgery. 4-AP was evaluated on Inhibition of outward K+ current components. Application of 0.2 mM 4-AP to human atrial myocytes inhibited the non-inactivating component of outward K+ currents by >80%, compared to only 25% inhibition of the inactivating component.
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