Ca2+-mobility in the sarcoplasmic reticulum of ventricular myocytes is low.
The sarcoplasmic reticulum (SR) in ventricular myocytes contains releasable Ca(2+) for activating cellular contraction. Recent measurements of intra-SR (luminal) Ca(2+) suggest a high diffusive Ca(2+)-mobility constant (D(CaSR)). This could help spatially to unify SR Ca(2+)-content ([Ca(2+)](SRT)) a...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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2008
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| _version_ | 1797072190702616576 |
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| author | Swietach, P Spitzer, K Vaughan-Jones, R |
| author_facet | Swietach, P Spitzer, K Vaughan-Jones, R |
| author_sort | Swietach, P |
| collection | OXFORD |
| description | The sarcoplasmic reticulum (SR) in ventricular myocytes contains releasable Ca(2+) for activating cellular contraction. Recent measurements of intra-SR (luminal) Ca(2+) suggest a high diffusive Ca(2+)-mobility constant (D(CaSR)). This could help spatially to unify SR Ca(2+)-content ([Ca(2+)](SRT)) and standardize Ca(2+)-release throughout the cell. But measurements of localized depletions of luminal Ca(2+) (Ca(2+)-blinks), associated with local Ca(2+)-release (Ca(2+)-sparks), suggest D(CaSR) may actually be low. Here we describe a novel method for measuring D(CaSR). Using a cytoplasmic Ca(2+)-fluorophore, we estimate regional [Ca(2+)](SRT) from localized, caffeine-induced SR Ca(2+)-release. Caffeine microperfusion of one end of a guinea pig or rat myocyte diffusively empties the whole SR at a rate indicating D(CaSR) is 8-9 microm(2)/s, up to tenfold lower than previous estimates. Ignoring background SR Ca(2+)-leakage in our measurement protocol produces an artifactually high D(CaSR) (>40 microm(2)/s), which may also explain the previous high values. Diffusion-reaction modeling suggests that a low D(CaSR) would be sufficient to support local SR Ca(2+)-signaling within sarcomeres during excitation-contraction coupling. Low D(CaSR) also implies that [Ca(2+)](SRT) may readily become spatially nonuniform, particularly under pathological conditions of spatially nonuniform Ca(2+)-release. Local control of luminal Ca(2+), imposed by low D(CaSR), may complement the well-established local control of SR Ca(2+)-release by Ca(2+)-channel/ryanodine receptor couplons. |
| first_indexed | 2024-03-06T23:04:08Z |
| format | Journal article |
| id | oxford-uuid:6333d7ee-3137-40b5-a321-e6360c93d69d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:04:08Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:6333d7ee-3137-40b5-a321-e6360c93d69d2022-03-26T18:11:20ZCa2+-mobility in the sarcoplasmic reticulum of ventricular myocytes is low.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6333d7ee-3137-40b5-a321-e6360c93d69dEnglishSymplectic Elements at Oxford2008Swietach, PSpitzer, KVaughan-Jones, RThe sarcoplasmic reticulum (SR) in ventricular myocytes contains releasable Ca(2+) for activating cellular contraction. Recent measurements of intra-SR (luminal) Ca(2+) suggest a high diffusive Ca(2+)-mobility constant (D(CaSR)). This could help spatially to unify SR Ca(2+)-content ([Ca(2+)](SRT)) and standardize Ca(2+)-release throughout the cell. But measurements of localized depletions of luminal Ca(2+) (Ca(2+)-blinks), associated with local Ca(2+)-release (Ca(2+)-sparks), suggest D(CaSR) may actually be low. Here we describe a novel method for measuring D(CaSR). Using a cytoplasmic Ca(2+)-fluorophore, we estimate regional [Ca(2+)](SRT) from localized, caffeine-induced SR Ca(2+)-release. Caffeine microperfusion of one end of a guinea pig or rat myocyte diffusively empties the whole SR at a rate indicating D(CaSR) is 8-9 microm(2)/s, up to tenfold lower than previous estimates. Ignoring background SR Ca(2+)-leakage in our measurement protocol produces an artifactually high D(CaSR) (>40 microm(2)/s), which may also explain the previous high values. Diffusion-reaction modeling suggests that a low D(CaSR) would be sufficient to support local SR Ca(2+)-signaling within sarcomeres during excitation-contraction coupling. Low D(CaSR) also implies that [Ca(2+)](SRT) may readily become spatially nonuniform, particularly under pathological conditions of spatially nonuniform Ca(2+)-release. Local control of luminal Ca(2+), imposed by low D(CaSR), may complement the well-established local control of SR Ca(2+)-release by Ca(2+)-channel/ryanodine receptor couplons. |
| spellingShingle | Swietach, P Spitzer, K Vaughan-Jones, R Ca2+-mobility in the sarcoplasmic reticulum of ventricular myocytes is low. |
| title | Ca2+-mobility in the sarcoplasmic reticulum of ventricular myocytes is low. |
| title_full | Ca2+-mobility in the sarcoplasmic reticulum of ventricular myocytes is low. |
| title_fullStr | Ca2+-mobility in the sarcoplasmic reticulum of ventricular myocytes is low. |
| title_full_unstemmed | Ca2+-mobility in the sarcoplasmic reticulum of ventricular myocytes is low. |
| title_short | Ca2+-mobility in the sarcoplasmic reticulum of ventricular myocytes is low. |
| title_sort | ca2 mobility in the sarcoplasmic reticulum of ventricular myocytes is low |
| work_keys_str_mv | AT swietachp ca2mobilityinthesarcoplasmicreticulumofventricularmyocytesislow AT spitzerk ca2mobilityinthesarcoplasmicreticulumofventricularmyocytesislow AT vaughanjonesr ca2mobilityinthesarcoplasmicreticulumofventricularmyocytesislow |