{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:44:20Z","timestamp":1783485860170,"version":"3.55.0"},"reference-count":67,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[1998,2,1]]},"abstract":"<jats:p>Wakamori, Minoru, Mark Strobeck, Tetsuhiro Niidome, Tetsuyuki Teramoto, Keiji Imoto, and Yasuo Mori. Functional characterization of ion permeation pathway in the N-type Ca<jats:sup>2+<\/jats:sup>channel. J. Neurophysiol. 79: 622\u2013634, 1998. Multiple types of high-voltage-activated Ca<jats:sup>2+<\/jats:sup>channels, including L-, N-, P-, Q- and R-types have been distinguished from each other mainly employing pharmacological agents that selectively block particular types of Ca<jats:sup>2+<\/jats:sup>channels. Except for the dihydropyridine-sensitive L-type Ca<jats:sup>2+<\/jats:sup>channels, electrophysiological characterization has yet to be conducted thoroughly enough to biophysically distinguish the remaining Ca<jats:sup>2+<\/jats:sup>channel types. In particular, the ion permeation properties of N-type Ca<jats:sup>2+<\/jats:sup>channels have not been clarified, although the kinetic properties of both the L- and N-type Ca<jats:sup>2+<\/jats:sup>channels are relatively well described. To establish ion conducting properties of the N-type Ca<jats:sup>2+<\/jats:sup>channel, we examined a homogeneous population of recombinant N-type Ca<jats:sup>2+<\/jats:sup>channels expressed in baby hamster kidney cells, using a conventional whole cell patch-clamp technique. The recombinant N-type Ca<jats:sup>2+<\/jats:sup>channel, composed of the \u03b1<jats:sub>1B<\/jats:sub>, \u03b1<jats:sub>2a<\/jats:sub>, and \u03b2<jats:sub>1a<\/jats:sub>subunits, displayed high-voltage-activated Ba<jats:sup>2+<\/jats:sup>currents elicited by a test pulse more positive than \u221230 mV, and were strongly blocked by the N-type channel blocker \u03c9-conotoxin-GVIA. In the presence of 110 mM Ba<jats:sup>2+<\/jats:sup>, the unitary current showed a slope conductance of 18.2 pS, characteristic of N-type channels. Ca<jats:sup>2+<\/jats:sup>and Sr<jats:sup>2+<\/jats:sup>resulted in smaller ion fluxes than Ba<jats:sup>2+<\/jats:sup>, with the ratio 1.0:0.72:0.75 of maximum conductance in current-voltage relationships of Ba<jats:sup>2+<\/jats:sup>, Ca<jats:sup>2+<\/jats:sup>, and Sr<jats:sup>2+<\/jats:sup>currents, respectively. In mixtures of Ba<jats:sup>2+<\/jats:sup>and Ca<jats:sup>2+<\/jats:sup>, where the Ca<jats:sup>2+<\/jats:sup>concentration was steadily increased in place of Ba<jats:sup>2+<\/jats:sup>, with the total concentration of Ba<jats:sup>2+<\/jats:sup>and Ca<jats:sup>2+<\/jats:sup>held constant at 3 mM, the current amplitude went through a clear minimum when 20% of the external Ba<jats:sup>2+<\/jats:sup>was replaced by Ca<jats:sup>+2<\/jats:sup>. This anomalous mole fraction effect suggests an ion-binding site where two or more permeant ions can sit simultaneously. By using an external solution containing 110 mM Na<jats:sup>+<\/jats:sup>without polyvalent cations, inward Na<jats:sup>+<\/jats:sup>currents were evoked by test potentials more positive than \u221250 mV. These currents were activated and inactivated in a kinetic manner similar to that of Ba<jats:sup>2+<\/jats:sup>currents. Application of inorganic Ca<jats:sup>2+<\/jats:sup>antagonists blocked Ba<jats:sup>2+<\/jats:sup>currents through N-type channels in a concentration-dependent manner. The rank order of inhibition was La<jats:sup>3+<\/jats:sup>\u2265 Cd<jats:sup>2+<\/jats:sup>\u226b Zn<jats:sup>2+<\/jats:sup>&gt; Ni<jats:sup>2+<\/jats:sup>\u2265 Co<jats:sup>2+<\/jats:sup>. When a short strong depolarization was applied before test pulses of moderate depolarizing potentials, relief from channel blockade by La<jats:sup>3+<\/jats:sup>and Cd<jats:sup>2+<\/jats:sup>and subsequent channel reblocking was observed. The measured rate (2 \u00d7 10<jats:sup>8<\/jats:sup>M<jats:sup>\u22121<\/jats:sup>s<jats:sup>\u22121<\/jats:sup>) of reblocking approached the diffusion-controlled limit. These results suggest that N-type Ca<jats:sup>2+<\/jats:sup>channels share general features of a high affinity ion-binding site with the L-type Ca<jats:sup>2+<\/jats:sup>channel, and that this site is easily accessible from the outside of the channel pore.<\/jats:p>","DOI":"10.1152\/jn.1998.79.2.622","type":"journal-article","created":{"date-parts":[[2017,12,25]],"date-time":"2017-12-25T07:07:11Z","timestamp":1514185631000},"page":"622-634","source":"Crossref","is-referenced-by-count":53,"title":["Functional Characterization of Ion Permeation Pathway in the N-Type Ca<sup>2+<\/sup>Channel"],"prefix":"10.1152","volume":"79","author":[{"given":"Minoru","family":"Wakamori","sequence":"first","affiliation":[{"name":"Department of Information Physiology, National Institute for Physiological Sciences, Okazaki, Aichi 444, Japan;"},{"name":"Institute of Molecular Pharmacology and Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0828; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Strobeck","sequence":"additional","affiliation":[{"name":"Department of Information Physiology, National Institute for Physiological Sciences, Okazaki, Aichi 444, Japan;"},{"name":"Institute of Molecular Pharmacology and Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0828; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuhiro","family":"Niidome","sequence":"additional","affiliation":[{"name":"Eisai Tsukuba Research Laboratories, Tsukuba, Ibaraki 300-26, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuyuki","family":"Teramoto","sequence":"additional","affiliation":[{"name":"Eisai Tsukuba Research Laboratories, Tsukuba, Ibaraki 300-26, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Imoto","sequence":"additional","affiliation":[{"name":"Department of Information Physiology, National Institute for Physiological Sciences, Okazaki, Aichi 444, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Information Physiology, National Institute for Physiological Sciences, Okazaki, Aichi 444, Japan;"},{"name":"Institute of Molecular Pharmacology and Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0828; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019396"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1989.sp017754"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1989.sp017610"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1984.sp015352"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90110-Y"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/308734a0"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.51.030189.002055"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/0079-6107(82)90011-6"},{"key":"B9","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/S0026-895X(25)09863-3","volume":"46","author":"Bloomenthal A. 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