{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:50:01Z","timestamp":1789552201118,"version":"build-2803163510"},"reference-count":48,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[1997,2,1]]},"abstract":"<jats:p> Tombaugh, Geoffrey C. and George G. Somjen. Differential sensitivity to intracellular pH among high- and low-threshold Ca<jats:sup>2+<\/jats:sup> currents in isolated rat CA1 neurons. J. Neurophysiol. 77: 639\u2013653, 1997. The effects of intracellular pH (pH<jats:sub>i<\/jats:sub>) on high-threshold (HVA) and low-threshold (LVA) calcium currents were examined in acutely dissociated rat hippocampal CA1 neurons with the use of the whole cell patch-clamp technique (21\u201323\u00b0C). Internal pH was manipulated by external exposure to the weak base NH<jats:sub>4<\/jats:sub>Cl or in some cases to the weak acid Na-acetate (20 mM) at constant extracellular pH (7.4). Confocal fluorescence measurements using the pH-sensitive dye SNARF-1 in both dialyzed and intact cells confirmed that NH<jats:sub>4<\/jats:sub>Cl caused a reversible alkaline shift. However, the external TEA-Cl concentration used during I <jats:sub>Ca<\/jats:sub> recording was sufficient to abolish cellular acidification upon NH<jats:sub>4<\/jats:sub>Cl wash out. With 10 mM N-2-hydroxyethylpiperazine- N\u2032-2-ethanesulfonic acid (HEPES) in the pipette, NH<jats:sub>4<\/jats:sub>Cl exposure reversibly enhanced HVA currents by 29%, whereas exposure to Na-acetate markedly and reversibly depressed HVA Ca currents by 62%. The degree to which NH<jats:sub>4<\/jats:sub>Cl enhanced HVA currents was inversely related to the internal HEPES concentration but was unaffected when internal ethylene glycol-bis(\u03b2-aminoethyl ether)- N,N,N\u2032,N\u2032-tetraacetic acid (EGTA) was replaced by equimolar bis-( o-aminophenoxy)- N,N,N\u2032,N\u2032-tetraacetic acid (BAPTA). When depolarizing test pulses were applied shortly after break-in ( V <jats:sub>h<\/jats:sub> = \u2212100 mV), NH<jats:sub>4<\/jats:sub>Cl caused a proportionally greater increase in the sustained current relative to the peak. The dihydropyridine Ca channel antagonist nifedipine (5 \u03bcM) blocked nearly all of this sustained current. A slowly inactivating nifedipine-sensitive (L-type) HVA current could be evoked from a depolarized holding potential of \u221250 mV; NH<jats:sub>4<\/jats:sub>Cl enhanced this current by 40 \u00b1 3% (mean \u00b1 SE) and reversibly shifted the tail-current activation curve by +6\u20138 mV. L-type currents exhibited more rapid rundown than N-type currents; HVA currents remaining after prolonged cell dialysis, or in the presence of nifedipine, inactivated rapidly and were depressed by \u03c9-conotoxin (GVIA). NH<jats:sub>4<\/jats:sub>Cl enhanced these N-type currents by 76 \u00b1 9%. LVA Ca currents were observed in 32% of the cells and exhibited little if any rundown. These amiloride-sensitive currents activated at voltages negative to \u221250 mV, were enhanced by extracellular alkalosis and depressed by extracellular acidosis, but were unaffected by exposure to either NH<jats:sub>4<\/jats:sub>Cl or NaAC. These results demonstrate that HVA Ca currents in hippocampal CA1 neurons are bidirectionally modulated by internal pH shifts, and that N-type currents are more sensitive to alkaline shifts than are L- or T-type (N &gt; L &gt; T). Our findings strengthen the idea that distinct cellular processes governed by different Ca channels may be subject to selective modulation by uniform shifts in cytosolic pH. <\/jats:p>","DOI":"10.1152\/jn.1997.77.2.639","type":"journal-article","created":{"date-parts":[[2017,12,25]],"date-time":"2017-12-25T01:01:17Z","timestamp":1514163677000},"page":"639-653","source":"Crossref","is-referenced-by-count":100,"title":["Differential Sensitivity to Intracellular pH Among High- and Low-Threshold Ca<sup>2+<\/sup> Currents in Isolated Rat CA1 Neurons"],"prefix":"10.1152","volume":"77","author":[{"given":"Geoffrey C.","family":"Tombaugh","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George G.","family":"Somjen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1994.63041477.x"},{"key":"B2","first-page":"1578","volume":"21","author":"Avery R. 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