The Editorial Office

Re: manuscript No. ***

Dear Dr.***

Thank you for your letter about our manuscript. And please find enclosed a manuscript entitled "Title" by author et al., which is the revised version of our previously submitted manuscript (****), and a floppy disk formatted by Macintosh computer. The altered points according to the comments are listed on attached papers.

We hope our responses are satisfactory ones for you. We are looking forward to your favorable consideration.

Yours sincerely,

Answers for comments raised by referee

Thank you for comments. In general, our explanations might be poor because of our lack of 'a sense of English'. We tried to make our manuscript better one according to your suggestions.

1. Title:

We changed the title as suggested.

2. Effect of Ca2+ depletion:

The effects of drugs used here are basically the same in case of extracellular Ca2+-free condition. But without Ca2+, the ATP-induced response decreased gradually as previously reported (Uneyama et al., 1993b), so it is not a good model system. We added the explanation about this experiments in the discussion (p9, second paragraph)

3. Discriminate between the intracellular and plasmamembrane Ca-pump:

As we mentioned in discussion (p11, l21), megakaryocyte has unique feature as a progenitor cell of platelet. Megakaryocyte has a lot of membrane systems in the cytoplasm which will become platelet plasma membrane. This fact made us impossible to declare the intracellular Ca2+ pump of megakaryocyte as "SERCA-pumps". At least, megakaryocyte is not a typical cell that possesses clearly distinguishable SERCA- and PMCA-pumps.

4. Not show effects of thapsigargin although refer to it:

We corrected the sentences (p6, l7 of the last paragraph).

5. Spontaneous effect of 1ｵM CPA:

The reason why we did not use the words "plasmamembrane Ca2+-pump" and "sarcoplasmic/endoplasmic reticulum Ca2+-pump" is in the answer for Q3. In addition, 1 ｵM of CPA induce Ca2+ rise in the absence of extracellular Ca2+. We already examined the effects of many drugs on megakaryocyte in extracellular Ca2+-free condition, and most of the results were the same in the presence of extracellular Ca2+. This 'tolerance' might be caused by the relative small area of the plasma membrane compared to the total cellular membrane systems in megakaryocyte. Anyway, we can not use the word "plasma membrane" and "SR/ER membrane" in megakaryocytes as other typical cells.

6. Difference between plateau-like and transient current:

We use the word "plateau-like" to mean "oscillatory pattern is disrupted as the increased Ca2+ level did not returned to basal level". The most important feature is "disruption of Ca2+-lowering process". Our explanations were not enough, we added some sentence (p6, l17). In our model of ATP-induced IKCa oscillation of megakaryocyte, the first spike is usually the biggest one, and then attenuate gradually. The time course of desensitization varies cell to cell. Thus the transformed current type partially depends on the features of individual cell. Though the difference between drug effects may be present, it should be investigated as another theme.

7. English:

Corrected as suggested, and rechecked.

8. Miss of ref.:

The missing issue and pages were added.