{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:43:12Z","timestamp":1779342192593,"version":"3.51.4"},"reference-count":0,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[1982,8,1]],"date-time":"1982-08-01T00:00:00Z","timestamp":397008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[1982,8]]},"abstract":"1. The effects of low concentrations of Cs+<\/jats:sup> (0\u00b701\u20103mM) on the fully activated I-V<\/jats:italic> relation \u012b<\/jats:italic>f<\/jats:sub>(E<\/jats:italic>) for the pace\u2010maker current in calf Purkinje fibres have been investigated. The action of Cs+<\/jats:sup> is two\u2010fold: in the negative region of the I-V<\/jats:italic> curve Cs+<\/jats:sup> induces a channel blockade; on the other hand, at more positive potentials Cs+<\/jats:sup> can produce the opposite effect, i.e. a current increase.<\/jats:p>2. Cs+<\/jats:sup>\u2010induced blockade is concentration\u2010 and voltage\u2010dependent, as observed on other cation channels. Data in the far negative voltage range (about \u2010 150 to \u2010 50 mV) can be fitted by a simple block model (Woodhull, 1973), which gives a mean value of 0\u00b771 for the fraction of membrane thickness (\u03b4) crossed by Cs+<\/jats:sup> ions before reaching the blocking site. The value of \u03b4 does not appear to be affected by either external Na or external K concentrations. Values for the dissociation constant of the blocking reaction at E<\/jats:italic> = 0 mV (k<\/jats:italic>0<\/jats:sub>) are found in the range 0\u00b75\u20103\u00b77 mM. In the positive region of the \u012b<\/jats:italic>f<\/jats:sub>(E<\/jats:italic>) relation the current depression caused by channel blockade vanishes. Unexpectedly, in this range the current can be observed to increase with Cs+<\/jats:sup>, and \u012b<\/jats:italic>f<\/jats:sub>(E<\/jats:italic>) curves in different Cs+<\/jats:sup> concentrations show cross\u2010over.<\/jats:p>3. Changing external K+<\/jats:sup> also produces similar cross\u2010over phenomena. Investigation of this effect reveals that the increase in slope of the I-V<\/jats:italic> curve on raising the external K+<\/jats:sup> concentration follows Michaelis\u2014Menten kinetics, and can be interpteted in terms of K+<\/jats:sup>\u2010induced channel activation. It is found that 44\u00b16 mM\u2010K+<\/jats:sup> half\u2010saturates the channel activating reaction.<\/jats:p>4. The Cs+<\/jats:sup>\u2010induced current increase is large in low\u2010K+<\/jats:sup> solutions and vanishes in high\u2010K+<\/jats:sup> solutions, suggesting a competition between Cs+<\/jats:sup> and K+<\/jats:sup> ions in their activating action. Increasing Na+<\/jats:sup> also limits the Cs+<\/jats:sup>\u2010induced current increase.<\/jats:p>5. Rb+<\/jats:sup> also blocks the i<\/jats:italic>f<\/jats:sub> channel, though less efficiently than Cs+<\/jats:sup>. The block caused by Rb+<\/jats:sup> is, unlike that of Cs+<\/jats:sup>, nearly voltage\u2010independent, and is explained by assuming that the blocking reaction occurs near the external mouth of the channel (mean value of \u03b4 is 0\u00b705). The zero\u2010voltage dissociation constant (k<\/jats:italic>0<\/jats:sub>) of the Rb+<\/jats:sup>\u2010blocking reaction ranges between 1\u00b74 and 5\u00b74 mM, and is lower in low\u2010Na+<\/jats:sup>, high\u2010K+<\/jats:sup> solutions.<\/jats:p>6. A possible characterization of the i<\/jats:italic>f<\/jats:sub> channel which explains these results includes an inner \u2018blocking\u2019 site, to which external Cs+<\/jats:sup> ions bind, blocking the channel, and a more external \u2018activatory\u2019 site, to which K+<\/jats:sup>, Cs+<\/jats:sup>, Rb+<\/jats:sup> and possibly Na+<\/jats:sup> ions bind. Binding of K+<\/jats:sup> to this site induces a current increase either by modulating the channel, or actually by opening the channel itself. A similar mechanism can apply to Cs+<\/jats:sup> and to Rb+<\/jats:sup> binding.<\/jats:p>","DOI":"10.1113\/jphysiol.1982.sp014315","type":"journal-article","created":{"date-parts":[[2014,12,19]],"date-time":"2014-12-19T07:02:56Z","timestamp":1418972576000},"page":"485-507","source":"Crossref","is-referenced-by-count":124,"title":["Block and activation of the pace\u2010maker channel in calf Purkinje fibres: effects of potassium, caesium and rubidium"],"prefix":"10.1113","volume":"329","author":[{"given":"Dario","family":"DiFrancesco","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[1982,8]]},"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.1982.sp014315","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.1982.sp014315","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,5]],"date-time":"2023-11-05T06:33:58Z","timestamp":1699166038000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.1982.sp014315"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1982,8]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1982,8]]}},"alternative-id":["10.1113\/jphysiol.1982.sp014315"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.1982.sp014315","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[1982,8]]}}}