Ethacizin blockade of calcium channels: a test of the guarded receptor hypothesis.

Published

Journal Article

The effect on calcium channels of the sodium channel antagonist, ethacizin, was studied in isolated frog ventricular cells using the whole cell voltage-clamp methodology. Ethacizin was found to block inward calcium current in a frequency-, voltage-, and concentration-dependent manner. The frequency-dependent blocking properties were modeled by considering the drug interaction with a voltage-dependent mixture of calcium channels harboring either an accessible or an inaccessible binding site. With repetitive stimulation, the pulse-to-pulse reduction in peak current is shown to be exponential, with a rate linearly related to the interstimulus interval and the drug concentration. Observed frequency- and concentration-dependent blocks were consistent with the predictions of the model, and mixture-specific rate constants were estimated from these data. The negligible shift in channel inactivation and the reduction of apparent binding and unbinding rates with more polarized membrane potentials imply the active moiety of ethacizin blocks open channels and is trapped within the channel at resting membrane potentials. The binding rate at 0 mV is similar to that observed in studies of interactions of other open channel blocking agents with voltage- and ligand-gated channels.

Full Text

Duke Authors

Cited Authors

  • Starmer, CF; Undrovinas, AI; Scamps, F; Vassort, G; Nesterenko, VV; Rosenshtraukh, LV

Published Date

  • November 1989

Published In

Volume / Issue

  • 257 / 5 Pt 2

Start / End Page

  • H1693 - H1704

PubMed ID

  • 2556050

Pubmed Central ID

  • 2556050

Electronic International Standard Serial Number (EISSN)

  • 2163-5773

International Standard Serial Number (ISSN)

  • 0002-9513

Digital Object Identifier (DOI)

  • 10.1152/ajpheart.1989.257.5.h1693

Language

  • eng