Xenopus follicle-enclosed oocytes are endowed with purinergic receptors located in the follicular cell membrane; their stimulation by ATP elicits an electrical response that includes generation of a fast inward current (F(Cl)) carried by Cl(-). Here, it was found that mechanical stimulation of the follicle provoked a native electrical response named I(mec). This was dependent on coupling between oocyte and follicular cells, because I(mec) was eliminated by enzymatic defolliculation or application of uncoupling drugs, such as heptanol or carbenoxolone. Moreover, the characteristics of I(mec) suggested that it corresponded with opening of the Cl(-) channel involved in F(Cl). For example, I(mec) showed cross-talk with the membrane mechanism that activates the F(Cl) response and anionic selectivity similar to that displayed by F(Cl). Also like F(Cl), I(mec) was independent of extracellular or intracellular Ca(2+). Furthermore, I(mec) was inhibited by superfusion with a purinergic antagonist, suramin, or by an enzyme that rapidly hydrolyzes ATP, apyrase. The response to mechanical stimulation was reconstituted in defolliculated oocytes expressing P2X channels as an ATP sensor. Recently, it has been shown that ATP release from the Xenopus oocyte is triggered by mechanical stimulation. Together, these observations seemed to indicate that I(mec) is activated through a mechanism that involves oocyte release of ATP that diffuses and activates purinergic receptors in follicular cells, with subsequent opening of F(Cl) channels. Thus, I(mec) generation disclosed a paracrine communication system via ATP between the oocyte and its companion follicular cells that might be of physiological importance during the growth and development of the gamete.
mortality than at 2 months or later. At 2 months they often die suddenly without clear symptoms of HF, whereas at 3 months, many of them showed evident symptoms of HF. In isolated left ventricular myocardium (LV) from 2 month-mice, spontaneous activity frequently occurred and action potential duration was prolonged. Transient outward (I to) and ultrarapid delayed rectifier K þ currents (I Kur) were significantly reduced in DCM myocytes. Correspondingly, down-regulation of Kv4.2, Kv1.5 and KChIP2 was evident in mRNA and protein levels. In 3 month-LV, more frequent spontaneous activity and further down-regulation in above K þ channels were observed. 1 month mice, on the contrary, showed infrequent spontaneous activity in LV, in which Kv4.2 but not Kv1.5 or KChIP2 was down-regulated. Because they are at low risk of death in spite of enlarged hearts, reduction in Kv4.2 is not sufficient for sudden death (SD). Our results suggest that the combined down-regulation of Kv4.2, Kv1.5 and KChIP2 prior to the onset of HF may play an important role in the premature SD in this DCM model.
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