{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T19:25:03Z","timestamp":1751052303810},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2981,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2000,12]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The hypothesis whether or not 4\u2010AP can affect vascular smooth muscle BK<jats:sub>Ca<\/jats:sub> currents was tested using the patch\u2010clamp technique, pH\u2010 and calcium\u2010fluorimetry, and freshly isolated rat arterial smooth muscle cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Application of 4\u2010AP reversibly inhibited BK<jats:sub>Ca<\/jats:sub> currents at an intracellular calcium ([Ca]<jats:sub>i<\/jats:sub>) of 250\u2003n<jats:sc>M<\/jats:sc> with a half\u2010block of 2.5\u2003m<jats:sc>M<\/jats:sc> at +50\u2003mV.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The presence of 2\u2003\u03bc<jats:sc>M<\/jats:sc> thapsigargin, 10\u2003\u03bc<jats:sc>M<\/jats:sc> heparin, and 10\u2003\u03bc<jats:sc>M<\/jats:sc> ryanodine did not alter the effect of 4\u2010AP on BK<jats:sub>Ca<\/jats:sub> currents at [Ca]<jats:sub>i<\/jats:sub> 250\u2003n<jats:sc>M<\/jats:sc>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>At [Ca]<jats:sub>i<\/jats:sub>&lt;100\u2003n<jats:sc>M<\/jats:sc> 4\u2010AP did not inhibit BK<jats:sub>Ca<\/jats:sub> currents.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Application of 4\u2010AP to the intracellular or extracellular side of excised BK<jats:sub>Ca<\/jats:sub> channels did not alter channel activity or channel amplitude.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Replacement of the pH\u2010sensitive calcium buffer EGTA by the pH\u2010insensitive calcium buffer BAPTA in the intracellular solution turned the 4\u2010AP\u2010induced inhibition of BK<jats:sub>Ca<\/jats:sub> currents into a stimulation at [Ca]<jats:sub>i<\/jats:sub> 250\u2003n<jats:sc>M<\/jats:sc>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Application of 4\u2010AP to single cells increased intracellular pH, which was accompanied by a reduction of [Ca]<jats:sub>i<\/jats:sub> in EGTA\u2010loaded cells and a stable [Ca]<jats:sub>i<\/jats:sub> in BAPTA\u2010loaded cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Thus, these results suggest that in isolated vascular smooth muscle cells at [Ca]<jats:sub>i<\/jats:sub>&gt;100\u2003n<jats:sc>M<\/jats:sc> 4\u2010AP affects BK<jats:sub>Ca<\/jats:sub> currents <jats:italic>via<\/jats:italic> an alteration of intracellular pH.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2000) <jats:bold>131<\/jats:bold>, 1643\u20131650; 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