{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T11:32:02Z","timestamp":1751974322739,"version":"3.41.0"},"reference-count":36,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[1999,3,1]]},"abstract":"<jats:p>Agents that block many types of K<jats:sup>+<\/jats:sup>channels (e.g., the aminopyridines) have substantial inotropic effects in skeletal muscle. Specific blockers of ATP-sensitive and Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup>channels, on the other hand, do not, or minimally, alter the force of nonfatigued muscle, consistent with a predominant role for voltage-gated K<jats:sup>+<\/jats:sup>channels in regulating muscle force. To test this more directly, we examined the effects of peptide toxins, which in other tissues specifically block voltage-gated K<jats:sup>+<\/jats:sup>channels, on rat diaphragm in vitro. Twitch force was increased in response to \u03b1-, \u03b2-, and \u03b3-dendrotoxin and tityustoxin K\u03b1 (17 \u00b1 6, 22 \u00b1 5, 42 \u00b1 14, and 13 \u00b1 5%; P &lt; 0.05, &lt; 0.01, &lt; 0.05, &lt; 0.05, respectively) but not in response to \u03b4-dendrotoxin or BSA (in which toxins were dissolved). Force during 20-Hz stimulation was also increased significantly by \u03b1-, \u03b2-, and \u03b3-dendrotoxin and tityustoxin K\u03b1. Among agents, increases in twitch force correlated with the degree to which contraction time was prolonged ( r = 0.88, P &lt; 0.02). To determine whether inotropic effects could be maintained during repeated contractions, muscle strips underwent intermittent 20-Hz train stimulation for a duration of 2 min in presence or absence of \u03b3-dendrotoxin. Force was significantly greater with than without \u03b3-dendrotoxin during repetitive stimulation for the first 60 s of repetitive contractions. Despite the \u223c55% higher value for initial force in the presence vs. absence of \u03b3-dendrotoxin, the rate at which fatigue occurred was not accelerated by the toxin, as assessed by the amount of time over which force declined by 25 and 50%. These data suggest that blocking voltage-activated K<jats:sup>+<\/jats:sup>channels may be a useful therapeutic strategy for augmenting diaphragm force, provided less toxic blockers of these channels can be found.<\/jats:p>","DOI":"10.1152\/jappl.1999.86.3.1009","type":"journal-article","created":{"date-parts":[[2017,12,22]],"date-time":"2017-12-22T14:31:38Z","timestamp":1513953098000},"page":"1009-1016","source":"Crossref","is-referenced-by-count":9,"title":["Peptide toxin blockers of voltage-sensitive K<sup>+<\/sup>channels: inotropic effects on diaphragm"],"prefix":"10.1152","volume":"86","author":[{"given":"Erik","family":"van Lunteren","sequence":"first","affiliation":[{"name":"Departments of Medicine and Neurosciences, Cleveland Veterans Affairs Medical Center and Case Western Reserve University, Cleveland, Ohio 44106"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Moyer","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Neurosciences, Cleveland Veterans Affairs Medical Center and Case Western Reserve University, Cleveland, Ohio 44106"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1988.tb11424.x"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1993.sp019637"},{"key":"B3","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/S0026-895X(25)09347-2","volume":"34","author":"Benishin C. 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