Publications by authors named "K Gerzon"

Comparative molecular field analysis (CoMFA) was used to analyze the relationship between the structure of a group of ryanoids and the modulation of the calcium channel function of the ryanodine receptor. The conductance properties of ryanodine receptors purified from sheep heart were measured using the planar, lipid bilayer technique. The magnitude of the ryanoid-induced fractional conductance was strongly correlated to specific structural loci on the ligand.

View Article and Find Full Text PDF

We have examined the effects of a number of derivatives of ryanodine on K+ conduction in the Ca2+ release channel purified from sheep cardiac sarcoplasmic reticulum (SR). In a fashion comparable to that of ryanodine, the addition of nanomolar to micromolar quantities to the cytoplasmic face (the exact amount depending on the derivative) causes the channel to enter a state of reduced conductance that has a high open probability. However, the amplitude of that reduced conductance state varies between the different derivatives.

View Article and Find Full Text PDF

The plant alkaloids ryanodine and dehydroryanodine are high affinity, biphasic modulators of the intracellularly located, calcium-regulated calcium release channels of a variety of cell types. To date, little is certain about the molecular basis of the interactions that prompt low concentrations of ryanodine (nanomolar to low micromolar) to activate (open) the channels and higher concentrations to deactivate (functionally close) the sarcoplasmic reticulum calcium release channel. In the present study, we approached this question using novel, semi-synthetic C10-Oeq ester derivatives of ryanodine and dehydroryanodine as molecular probes of the ryanodine binding sites on the calcium release channel.

View Article and Find Full Text PDF

The plant alkaloids ryanodine and dehydroryanodine are specific and potent modulators of the sarcoplasmic reticulum calcium release channel. In the present study, acidic, basic, and neutral side chains esters of these diterpene compounds were prepared and their pharmacologic activities were assessed. Binding affinities of the novel C10-Oeq ester derivatives for the sarcoplasmic reticulum Ca2+ release channel were evaluated with sarcoplasmic reticular vesicles prepared from rabbit skeletal muscle.

View Article and Find Full Text PDF

An 125I-iodinated ryanodine analog, modified by attaching an iodo-Cbz-beta-alanyl group to the C10eq hydroxy of ryanodine (iodo-carbobenzyloxy-beta-alanyl-ryanodine), binds to cardiac sarcoplasmic reticulum Ca2+ release channels with equal affinity as [3H]ryanodine. In the present study, both iodo-Cbz-beta-alanyl-ryanodine and ryanodine bound to canine cardiac microsomal membrane preparations in a Ca2+ dependent manner. At 10 microM free Ca2+ doxorubicin increased specific binding of both ligands, with doxorubicin concentrations of 4.

View Article and Find Full Text PDF