Modulation of cardiac voltage-activated K currents by glypican 1 heparan sulfate proteoglycan.

BACKGROUND

Glypican 1 (Gpc1) is a heparan sulfate proteoglycan attached to the cell membrane via a glycosylphosphatidylinositol anchor, where it holds glycosaminoglycans nearby. We have recently shown that Gpc1 knockout (Gpc1) mice feature decreased systemic blood pressure. To date, none has been reported regarding the role of Gpc1 on the electrical properties of the heart and specifically, in regard to a functional interaction between Gpc1 and voltage-gated K channels.

METHODS

We used echocardiography and in vivo (electrocardiographic recordings) and in vitro (patch clamping) electrophysiology to study mechanical and electric properties of mice hearts. We used RT-PCR to probe K channels' gene transcription in heart tissue.

RESULTS

Gpc1 hearts featured increased cardiac stroke volume and preserved ejection fraction. Gpc1 electrocardiograms showed longer QT intervals, abnormalities in the ST segment, and delayed T waves, corroborated by longer action potentials in isolated ventricular cardiomyocytes. In voltage-clamp, these cells showed decreased I and I voltage-activated K current densities. Moreover, I showed activation at less negative voltages, but a higher level of inactivation at a given membrane potential. Kcnh2 and Kcnq1 voltage-gated K channels subunits' transcripts were remarkably more abundant in heart tissues from Gpc1 mice, suggesting that Gpc1 may interfere in the steps between transcription and translation in these cases.

CONCLUSION

Our data reveals an unprecedented connection between Gpc1 and voltage-gated K channels expressed in the heart and this knowledge contributes to the understanding of the role of this HSPG in cardiac function which may play a role in the development of cardiovascular disease.