Apico–basal inhomogeneity in distribution of ion channels in canine and human ventricular myocardium

Abstract

Objectives: The aim of the present study was to compare the apico–basal distribution of ion currents and the underlying ion channel proteins in canine and human ventricular myocardium.

Methods: Ion currents and action potentials were recorded in canine cardiomyocytes, isolated from both apical and basal regions of the heart, using whole-cell voltage clamp techniques. Density of channel proteins in canine and human ventricular myocardium was determined by Western blotting.

Results: Action potential duration was shorter and the magnitude of phase-1 repolarization was significantly higher in apical than basal canine myocytes. No differences were observed in other parameters of the action potential or cell capacitance. Amplitude of the transient outward K⁺ current (29.6 ± 5.7 versus 16.5 ± 4.4 pA/pF at +65 mV) and the slow component of the delayed rectifier K⁺ current (5.61 ± 0.43 versus 2.14 ± 0.18 pA/pF at +50 mV) were significantly larger in apical than in basal myocytes. Densities of the inward rectifier K⁺ current, rapid delayed rectifier K⁺ current, and L-type Ca²⁺ current were similar in myocytes of apical and basal origin. Apico–basal differences were found in the expression of only those channel proteins which are involved in mediation of the transient outward K⁺ current and the slow delayed rectifier K⁺ current: expression of Kv1.4, KChIP2, KvLQT1 and MinK was significantly higher in apical than in basal myocardium in both canine and human hearts.

Conclusions: The results suggest that marked apico–basal electrical inhomogeneity exists in the canine–and probably in the human–ventricular myocardium, which may result in increased dispersion, and therefore, cannot be ignored when interpreting ECG recordings, pathological alterations, or drug effects.

Ion channels, K-channel, Membrane currents, Membrane potential, Myocytes