{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:28:52Z","timestamp":1789187332933,"version":"build-2803163510"},"reference-count":0,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[1992,4,1]],"date-time":"1992-04-01T00:00:00Z","timestamp":702086400000},"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":[[1992,4]]},"abstract":"<jats:p>1. The whole\u2010cell patch clamp technique was employed to study the effects of the beta\u2010agonist isoprenaline (ISO) on the Na(+)=K+ pump current, Ip, in acutely isolated ventricular myocytes from guinea\u2010pig hearts. Propranolol, a beta\u2010adrenergic antagonist, was used to demonstrate that all of the effects of ISO, stimulatory or inhibitory, are mediated by beta\u2010receptors. 2. Below about 150 nM [Ca2+]i, we find that ISO reduces Ip, while above this [Ca2+]i ISO increases Ip. The stimulatory and inhibitory effects of ISO on Ip are independent of either intracellular sodium ([Na+]i) or extracellular potassium ([K+]o). These results suggest that the end\u2010effect of ISO is directly on the maximum pump turnover rate (Vmax) rather than indirectly through changes in [Na+]i or [K+]o or modulatory effects on Na+ or K+ affinity. 3. The maximum effect of ISO increases Ip by 25% when [Ca2+] is buffered at 1.4 microM. A half\u2010maximal effect is reached at roughly 10 nM\u2010ISO and a near\u2010maximal effect by 0.5 microM. 4. The permeabilized patch technique, using amphotericin B (Horn &amp; Marty, 1988; Rae, Cooper, Gates &amp; Watsky, 1991), was employed to minimize changes in the normal second messenger systems and calcium buffers. In these experiments, we used a high intracellular sodium solution (pipette sodium was 50 mM), thus sodium\u2010calcium exchange was depressed and we expected [Ca2+]i to be above 150 nM. ISO increases Ip in these conditions as in the dialysed cells. 5. Our results suggest that beta\u2010stimulation can increase Ip, but only if [Ca2+]i is above about 150 nM. In the beating heart [Ca2+]i rises well above this value during systole and the average [Ca2+]i, which depends on heart rate, is expected to normally be above this level. During beta\u2010stimulation, the increase in Ip along with a concomitant increase in IK (Giles, Nakajima, Ono &amp; Shibata, 1989; Duchatelle\u2010Gourdon, Hartzell &amp; Lagrutta, 1989) helps prevent action potential lengthening and allows an increase in heart rate even in the presence of increased calcium current. Further, beta\u2010stimulation will compensate for the effects on Ip of either hypokalaemia or digitalis toxicity, and so reduce the expected rise in both [Na+]i and [Ca2+]i.<\/jats:p>","DOI":"10.1113\/jphysiol.1992.sp019109","type":"journal-article","created":{"date-parts":[[2014,12,17]],"date-time":"2014-12-17T16:24:46Z","timestamp":1418833486000},"page":"689-704","source":"Crossref","is-referenced-by-count":51,"title":["Isoprenaline, Ca2+ and the Na(+)\u2010K+ pump in guinea\u2010pig ventricular myocytes."],"prefix":"10.1113","volume":"449","author":[{"given":"J","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R T","family":"Mathias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I S","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G J","family":"Baldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[1992,4]]},"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.1992.sp019109","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.1992.sp019109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T17:13:56Z","timestamp":1698081236000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.1992.sp019109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,4]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1992,4]]}},"alternative-id":["10.1113\/jphysiol.1992.sp019109"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.1992.sp019109","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,4]]}}}