Cardiovascular Diseases Poster Session

Re: dr.S.Reading

S. Reading

On Tue Dec 15, kyselovic wrote
>could you explain whay you speculate that the positive inotropic effect of NO is mediated by an increase in
>the inward Ca2+ ion current via upregulation of L-type Ca2+ channels while you are just only block the channels

Thank you for your interest in our poster Dr. Kyuselovic. We believe that the positive inotropic effect of NO is mediated by changes in intracellular Ca2+ primarily because NO improved peak force without altering the time course characteristics of the isometric twitch contraction which would be expected if there was phosphorylation of the contractile proteins.(i.e. such as the case with a Beta adrenergic agonist where phosphorylation of troponin I decreases the time to peak force and contractile duration ,compare fig 3a and 3c)
  The blocker experiments were conducted to establish whether the extra or intracellular Ca2+ pools were responsible for the NO effect. When the sarcoplasmic reticulum Ca2+ release channels were blocked with ryanodine, NO improved peak force by almost 8% suggesting that the Ca2+ was coming from an extracellular source. To block inward movement of extracellular Ca2+ we used the L-type Ca2+ antagonist verapamil. Since NO was unable to effect peak force in the presence of verapamil we concluded that the positive inotropic effect of NO is related to the activity of the L-type Ca2+ channels. While this evidence is  indirect, there is some support in the literature that L-type Ca2+ channels can be stimulated by NO/cGMP. We are continuing our experiments to elucidate this phenomenon more completely. If you have additional comments or questions, feel free to contact me via email. I hope you have found the conference enjoyable and informative.
S. Reading

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