Apoptosis is responsible for normal tissue homeostasis and isknown to mediate pathological cell loss (Fulton, 1996;Nagata, 1997; Salvesen and Dixit, 1997; Wallach, 1997;Wyllie, 1998). Apoptosis is characterized by morphologicalchanges. These include cell body and nuclear breakdown,chromatin condensation and fragmentation, and formation ofapoptotic bodies (Erhardt and Cooper, 1996; Kothakota et al.,1997; Liu et al., 1997; Enari et al., 1998; Janicke et al., 1998a,b; Zheng et al., 1998; McIlroy et al., 1999; Sakahira et al.,1999; Zhang et al., 1999; D’Mello et al., 2000). Recently,molecular details of apoptosis was elucidated, and apoptoticgenes and proteins were increasingly characterized (Du et al.,2000; Srinivasula et al., 2000; Wu et al., 2000). Severalapoptotic-signaling pathways have been suggested. Receptor-mediated apoptosis is characterized by the formation of thedeath-inducing signaling complex (DISC), comprising the Fasreceptor, FADD, FLASH, procaspase-8 and other proteins(Minn et al., 1996; Muzio et al., 1996; Stennicke andSalvesen, 1997; Chen et al., 1998; Widmann et al., 1998; Yehet al., 1998). Procaspase-8 is processed to active caspase-8,which in turn cleaves downstream signaling proteins likeprocaspase-3. On the other hand, chemical-induced apoptosisgenerally leads to mitochondrial damage and the subsequentrelease of cytochrome c (Krippner et al., 1996; Chauhan et al.,1997; Kluck et al., 1997; Yang et al., 1997; Eskes et al., 1998;Bossy-Wetzel and Green, 1999; Fiers et al., 1999; Granville etal., 1998; Gross et al., 1999; Kluck et al., 1999; Martinou,1999; Schapira, 1999). This protein associates with Apaf-1,caspase-9 and dATP to form a multiprotein complex called theapoptosome (Li et al., 1997; Yang et al., 1997; Zou et al.,1997; Srinivasula et al., 1998; Chinnaiyan, 1999; Fujita et al.,1999; Hu et al., 1999; Krajewski et al., 1999; Stennicke et al.,1999; Zou et al., 1999; Cain et al., 2000; Purring-Koch andMcLendon, 2000). This complex acts as a kind ofholoenzyme that activates procaspase-3 and -7. DFF45/ICADis cleaved by active caspase-3 to release its complexed DNase,DFF40/CAD, which in turn degrades nuclear DNA (Liu et al.,1998; Zheng et al., 1998; Liu et al., 1999; McCarty et al.,1999; Wolf et al., 1999). Caspase-3 is also responsible for theprocessing of Acinus, a chromosomal condensation factor(Sahara et al., 1999). A cross-talk exists between the twoapoptotic pathways, which are not exclusive of each other.Caspase-8 cleaves Bid, which in turn acts on mitochondria torelease cytochrome c (Scaffidi et al., 1997; Juo et al., 1998;Luo et al., 1998; Srinivasan et al., 1998; Gross et al., 1999;Kluck et al., 1999; Lin et al., 1999; Sun et al., 1999; Tan etal., 1999; Zhuang et al., 1999; Liu et al., 2000). Conversely,caspase-3 and other downstream caspases activate procaspase-8 (Stennicke and Salvesen, 1997; Stennicke et al., 1998). Therequirement for this activation is unclear, but possibly occursto induce amplification of the apoptotic signal. Recently,caspase-12 was identified on endoplasmic recticulum (ER)(Nakagawa et al., 2000). The activation pathway of thecaspase was mediated by m-calpain, which suggests that thechange of the intracellular calcium concentration may be thetriggering signal. The caspase was also cleaved and activatedby caspase-7. This observation provides the link betweenchemical or receptor-mediated and ER-mediated apoptosis.However, until recently none of the caspase-12 substrateswere identified, except the caspase itself. How the caspaseinduces apoptosis remains to be elucidated.During apoptosis, several physiological changes areobserved. It is known that the pH in cells that undergoapoptosis drops. It is also known that calcium influx occursand potassium and chloride ions efflux in cells that undergoapoptosis (Bortner et al., 1997; Yu et al., 1997; Bortner andCidlowski, 1999). However, the molecular details of thephysiological changes are largely unknown. Recently severalreports have indicated the importance of the changes forensuring cell death. Here, the relationship between potassiumefflux and apoptosis is reviewed.