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- W1885337384 abstract "Phosphorylation of inositol 1,4,5‐trisphosphate receptors (InsP 3 R) by PKA represents an important, common route for regulation of Ca 2+ release. Following phosphorylation of the S2 splice variant of InsP 3 R‐1 (S2– InsP‐1), Ca 2+ release is markedly potentiated. In this study we utilize the plasma membrane (PM) expression of InsP 3 R‐1 and phosphorylation state mutant InsP 3 R‐1 to study how this regulation occurs at the single InsP 3 R‐1 channel level. DT40‐3KO cells stably expressing rat S2– InsP 3 R‐1 were generated and studied in the whole‐cell mode of the patch clamp technique. At hyperpolarized holding potentials, small numbers of unitary currents (average ∼1.7 per cell) were observed which were dependent on InsP 3 and the presence of functional InsP 3 R‐1, and regulated by both cytoplasmic Ca 2+ and ATP. Raising cAMP markedly enhanced the open probability ( P o ) of the InsP 3 R‐1 and induced bursting activity, characterized by extended periods of rapid channel openings and subsequent prolonged refractory periods. The activity, as measured by the P o of the channel, of a non‐phosphorylatable InsP 3 R‐1 construct (Ser1589Ala/Ser1755Ala InsP 3 R‐1) was markedly less than wild‐type (WT) InsP 3 R‐1 and right shifted some ∼15‐fold when the concentration dependency was compared to a phosphomimetic construct (Ser1589Glu/Ser1755Glu InsP 3 R‐1). No change in conductance of the channel was observed. This shift in apparent InsP 3 sensitivity occurred without a change in InsP 3 binding or Ca 2+ dependency of activation or inactivation. Biophysical analysis indicated that channel activity can be described by three states: an open state, a long lived closed state which manifests itself as long interburst intervals, and a short‐lived closed state. Bursting activity occurs as the channel shuttles rapidly between the open and short‐lived closed state. The predominant effect of InsP 3 R‐1 phosphorylation is to increase the likelihood of extended bursting activity and thus markedly augment Ca 2+ release. These analyses provide insight into the mechanism responsible for augmenting InsP 3 R‐1 channel activity following phosphorylation and moreover should be generally useful for further detailed investigation of the biophysical properties of InsP 3 R." @default.
- W1885337384 created "2016-06-24" @default.
- W1885337384 creator A5006672847 @default.
- W1885337384 creator A5014757696 @default.
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- W1885337384 date "2008-07-31" @default.
- W1885337384 modified "2023-10-18" @default.
- W1885337384 title "Regulation of single inositol 1,4,5-trisphosphate receptor channel activity by protein kinase A phosphorylation" @default.
- W1885337384 cites W1485726990 @default.
- W1885337384 cites W1486474082 @default.
- W1885337384 cites W1487968269 @default.
- W1885337384 cites W1539592459 @default.
- W1885337384 cites W1598081743 @default.
- W1885337384 cites W1729732610 @default.
- W1885337384 cites W1788868849 @default.
- W1885337384 cites W1973237558 @default.
- W1885337384 cites W1973646870 @default.
- W1885337384 cites W1974040612 @default.
- W1885337384 cites W1975085370 @default.
- W1885337384 cites W1976746355 @default.
- W1885337384 cites W1980166477 @default.
- W1885337384 cites W1986371114 @default.
- W1885337384 cites W1990441076 @default.
- W1885337384 cites W1995179004 @default.
- W1885337384 cites W1997144151 @default.
- W1885337384 cites W1997778815 @default.
- W1885337384 cites W1998828489 @default.
- W1885337384 cites W2003782545 @default.
- W1885337384 cites W2006442989 @default.
- W1885337384 cites W2008667203 @default.
- W1885337384 cites W2008726042 @default.
- W1885337384 cites W2009292667 @default.
- W1885337384 cites W2020828897 @default.
- W1885337384 cites W2021094409 @default.
- W1885337384 cites W2021847777 @default.
- W1885337384 cites W2024622938 @default.
- W1885337384 cites W2026187249 @default.
- W1885337384 cites W2026328003 @default.
- W1885337384 cites W2035786682 @default.
- W1885337384 cites W2036287496 @default.
- W1885337384 cites W2039599376 @default.
- W1885337384 cites W2045242383 @default.
- W1885337384 cites W2045399399 @default.
- W1885337384 cites W2046492840 @default.
- W1885337384 cites W2047244263 @default.
- W1885337384 cites W2048682543 @default.
- W1885337384 cites W2051402557 @default.
- W1885337384 cites W2052018007 @default.
- W1885337384 cites W2053714100 @default.
- W1885337384 cites W2059628577 @default.
- W1885337384 cites W2060802834 @default.
- W1885337384 cites W2063163622 @default.
- W1885337384 cites W2081082836 @default.
- W1885337384 cites W2082722322 @default.
- W1885337384 cites W2082908588 @default.
- W1885337384 cites W2089930510 @default.
- W1885337384 cites W2090407149 @default.
- W1885337384 cites W2092710223 @default.
- W1885337384 cites W2096199252 @default.
- W1885337384 cites W2099430463 @default.
- W1885337384 cites W2110499044 @default.
- W1885337384 cites W2112841338 @default.
- W1885337384 cites W2114264782 @default.
- W1885337384 cites W2119100472 @default.
- W1885337384 cites W2126293964 @default.
- W1885337384 cites W2142467481 @default.
- W1885337384 cites W2143843444 @default.
- W1885337384 cites W2144922739 @default.
- W1885337384 cites W2154411206 @default.
- W1885337384 cites W2155044464 @default.
- W1885337384 cites W2163191890 @default.
- W1885337384 cites W2165292955 @default.
- W1885337384 cites W2166691490 @default.
- W1885337384 cites W2268409607 @default.
- W1885337384 cites W2341412675 @default.
- W1885337384 cites W4242349879 @default.
- W1885337384 cites W4296759590 @default.
- W1885337384 doi "https://doi.org/10.1113/jphysiol.2008.152314" @default.
- W1885337384 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2538833" @default.
- W1885337384 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18535093" @default.
- W1885337384 hasPublicationYear "2008" @default.
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