10.1113\/jphysiol.1996.sp021522<\/a><\/p>\nAuthors:<\/h4>\n
A J Levi, Jia Li, Kenneth W. Spitzer, J H Bridge<\/p>\n
Abstract:<\/h4>\n
1. We used rapid solution changes to investigate the mechanisms which trigger Ca2+ release from the sarcoplasmic reticulum (SR) in guinea-pig ventricular myocytes. We patch-clamped myocytes at 36 degrees C and used indo-1 to monitor intracellular Ca2+. Before each test pulse, we established a standard level of SR Ca2+ load by applying a train of conditioning pulses. 2. We switched rapidly to 32 microM nifedipine (an L-type Ca2+ current (ICa,L) blocker) 8 s before a test pulse, and just after applying nifedipine we applied a ramp depolarization to pre-block Ca2+ channels. We found that ICa,L elicited by the following test pulse was inhibited almost completely (98-99% inhibition). 3. The indo-1 transient elicited by an 800 ms depolarizing pulse showed a rapid initial rise which was inhibited by ryanodine-thapsigargin. This indicated that the rapid rise was due to Ca2+ release from the SR, and therefore provides an index of SR Ca2+ release. 4. In cells dialysed internally with 10 mM Na(+)-containing solution, nifedipine application before a +10 mV test pulse blocked 62% of the rapid initial phase of the indo-1 transient. Calibration curves of indo-1 for intracellular Ca2+ (using a KD of indo-1 for Ca2+ of either 250 or 850 nM, the reported range) indicated that between 67 and 76% of the Ca2+i transient was inhibited by nifedipine. Thus, in cells dialysed with 10 mM Na+ and depolarized to +10 mV, and in the absence of ICa,L, this suggests that another trigger mechanism for SR release is able to trigger between 33 and 24% of the Ca2+i transient. 5. For a given dialysing Na+ concentration, the fraction of indo-1 transient which was inhibited by nifedipine decreased as test potential became more positive. In cells dialysed with 10 mM Na+ and pulsed to +110 mV, 24% of the rapid phase of the indo-1 transient was inhibited by nifedipine (equivalent to between 27 and 37% of the Ca2+i transient). 6. For a given test potential, the fraction of the indo-1 transient which was inhibited by nifedipine decreased as dialysing Na+ concentration increased. In cells dialysed with Na(+)-free solution and pulsed to +10 mV, 84% of the indo-1 transient was inhibited by nifedipine (equivalent to between 88 and 91% of the Ca2+i transient). In contrast, in cells dialysed with 20 mM Na+ and pulsed to +10 mV, 41% of the indo-1 transient was inhibited by nifedipine (equivalent to between 47 and 57% of the Ca2+i transient). 7. Dialysing cells with different Na+ concentrations could lead to a different SR Ca2+ content. We therefore manipulated the conditioning train before each test pulse to change the extent of SR loading. For each dialysing Na+ concentration, we found no change in the degree to which nifedipine blocked the indo-1 transient when SR content was either increased or decreased. 8. The results support the idea that both ICa, L and a second mechanism are able to trigger SR release and the resulting Ca2+i transient. When ICa, L was blocked with nifedipine, the fraction of Ca2+i transient which remained increased with more positive test potential and higher internal Na+. This is consistent with the hypothesis that the second SR trigger mechanism is Ca2+ entry via reverse Na(+)-Ca2+ exchange, elicited by a step change in membrane potential.<\/p>\n","protected":false},"excerpt":{"rendered":"
DOI: 10.1113\/jphysiol.1996.sp021522 Authors: A J Levi, Jia Li, Kenneth W. Spitzer, J H Bridge Abstract: 1. We used rapid solution changes to investigate the mechanisms which trigger Ca2+ release from the sarcoplasmic reticulum (SR) in guinea-pig ventricular myocytes. We patch-clamped myocytes at 36 degrees C and used indo-1 to monitor intracellular Ca2+. Before each test […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[21],"tags":[],"class_list":["post-795","post","type-post","status-publish","format-standard","hentry","category-rsc-200"],"_links":{"self":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/posts\/795","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=795"}],"version-history":[{"count":0,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/posts\/795\/revisions"}],"wp:attachment":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=795"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=795"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=795"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}