Dr. ****
Distributing Editor
Dear Dr. ****
Please find enclosed a manuscript entitled "Title" by ***. This manuscript is prepared according to your previous suggestion to resubmit a new paper after taking into account the criticisms made of MS ****. We thank you for your previous comments. The answer to the specific criticisms of a Reviewing Editor and an Expert Referee to MS ****, and a copy of comments we got previously were also enclosed.
We are looking forward to your favourable consideration.
The attached paper does not contain any material other than that submitted with this manuscript, which has been, or is intended to be published anywhere, except in The Journal of ***. It is understood that upon acceptance for publication the entire copyright in this paper shall pass to the *** Society.
Yours sincerely,
RESPONSE TO EDITOR
Thank you for your comments.
Major points:
One of the critical points you mentioned is about the comparison between conventional whole cell recording (WCR) and perforated patch recording (PPR). Our intention is to clarify the difference between the results obtained by **** (1990) and us. Thus, we were satisfied that we could get the same data as ****'s. In our previous manuscript, the tone of the sentence was somewhat exaggerated as a result of our immaturance. We rewrote the sentence, and added new data in Fig. 3 as you mentioned. The second point is about the pharmacology of the purinoceptor. We added new figures (Figs. 7 and 10) and discussed about them to answer your comment.
Small points:
1. The second and third paragraphs of the Introduction are difficult to follow and should be rewritten. ...
We have rewrote the 'Introduction' according to your suggestion. We hope the new version may be better than previous one.
2. Fig.1: Unit labels on vertical axes are missing in parts B, C and D.
The unit is 's' (seconds) and shown in the figure.
RESPONSE TO EXTERNAL REFEREE
Thank you for your comments.
Major points:
One of the major points raised by the referee is that the characterization of a type(s) of purinoceptor is rather week.We added new data (Fig. 7) which support that ATP and ADP act on the same purinoceptor. Newly added current traces in Fig. 10 also suggest this.Another point concerns the explanation of the advantages of perforated patch method.Our intention is to clarify the difference between the results obtained by **** (1990) and us. Thus, we were satisfied that we could get the same data as ****'s. In our previous manuscript, the tone of the sentence was somewhat exaggerated as a result of our immaturance. We rewrote the sentence, and added new data in Fig. 3.
Specific remarks:
1) It is better to rewrite "Introduction" as to fit the title.
We have rewritten the Introduction according to your suggestion. We hope the new version may be better than previous one.
2) In "Methods" the authors should describe the time course of the establishment of "perforated patch mode" ...
We added the descriptions as you suggested (p. 6).
3) In "Results" p.8. Under current-clamp condition, does not 10 µM ATP induce oscillatory hyperpolarization?, ...
ATP induce oscillatory hyperpolarization. The explanation was poor, thus we corrected the sentence (p. 8, last line).
4) In Fig. 1A, the base-line of current trace decreases by c.a. 50 pA after application of ATP. ...
The base lines sometimes drift slightly even in the absence of any stimulation. Thus, it is not an artifact of the Y-tube. We added a comment about this point in the text (p. 9, line 8 ).
5) In "Results", p.11, 2nd para, line 5, the sentence "EGTA competes with ...". ...
On this point, we added new experimental results in Fig. 3 and discussed in the text as mentioned in "Major points" (p.11, second para).
6) The ATP application period is somewhat strange in Fig. 3A, ..
.This was our mistake and corrected.
7) In "Results", p.12. The authors present data of various K+-channel inhibitors in the sub-section ...
This was our mistake, too.The sentence was deleted.
8) In "Results", p.15, 2nd sub-section and Fig. 7C. There are reports that ADP induces Ca2+-influx in platelets ..
The gradual attenuation shown in Fig. 7 may be a result of desensitization as mentioned in Fig. 1. The difference seen between a and c can be explained by the difference in cellular reactivity. We added a figure (Fig.9) to explain the apparent discrepancy between our's and Ikeda et al.'s results and discussed in detail in the text (pp. 16-17, 20). We think 10 µM of La3+ had no effect on ATP- and ADP-induced responses.
9) In "Discussion", the last part. The authors speculate without any firm evidence that ...
The sentences pointed out were deleted.
10) Discussion should be shortened by eliminating repeated sentences and those not directly relating to the study.
We improved the Discussion according to your suggestion.