TY - JOUR
T1 - Regulation of neuronal Na+/K+-atpase by specific protein kinases and protein phosphatases
AU - Mohan, Sandesh
AU - Tiwari, Manindra Nath
AU - Biala, Yoav
AU - Yaari, Yoel
N1 - Publisher Copyright:
© 2019 the authors.
PY - 2019/7/10
Y1 - 2019/7/10
N2 - The Na+/K+-ATPase (NKA) is a ubiquitous membrane-bound enzyme responsible for generating and maintaining the Na+ and K+ electrochemical gradients across the plasmalemma of living cells. Numerous studies in non-neuronal tissues have shown that this transport mechanism is reversibly regulated by phosphorylation/dephosphorylation of the catalytic α subunit and/or associated proteins. In neurons, Na+/K+ transport byNKAis essential for almost all neuronal operations,consumingupto two-thirds of the neuron’s energy expenditure. However, little is known about its cellular regulatory mechanisms. Here we have used an electrophysiological approach to monitor NKA transport activity in male rat hippocampal neurons in situ. We report that this activity is regulated by a balance between serine/threonine phosphorylation and dephosphorylation. Phosphorylation by the protein kinases PKG and PKC inhibits NKA activity, whereas dephosphorylation by the protein phosphatases PP-1 and PP-2B (calcineurin) reverses this effect. Given that these kinases and phosphatases serve as downstream effectors in key neuronal signaling pathways, theymaymediate the coupling of primary messengers, such as neurotransmitters, hormones, and growth factors, to the NKAs, through which multiple brain functions can be regulated or dysregulated.
AB - The Na+/K+-ATPase (NKA) is a ubiquitous membrane-bound enzyme responsible for generating and maintaining the Na+ and K+ electrochemical gradients across the plasmalemma of living cells. Numerous studies in non-neuronal tissues have shown that this transport mechanism is reversibly regulated by phosphorylation/dephosphorylation of the catalytic α subunit and/or associated proteins. In neurons, Na+/K+ transport byNKAis essential for almost all neuronal operations,consumingupto two-thirds of the neuron’s energy expenditure. However, little is known about its cellular regulatory mechanisms. Here we have used an electrophysiological approach to monitor NKA transport activity in male rat hippocampal neurons in situ. We report that this activity is regulated by a balance between serine/threonine phosphorylation and dephosphorylation. Phosphorylation by the protein kinases PKG and PKC inhibits NKA activity, whereas dephosphorylation by the protein phosphatases PP-1 and PP-2B (calcineurin) reverses this effect. Given that these kinases and phosphatases serve as downstream effectors in key neuronal signaling pathways, theymaymediate the coupling of primary messengers, such as neurotransmitters, hormones, and growth factors, to the NKAs, through which multiple brain functions can be regulated or dysregulated.
KW - Ca1 pyramidal cell
KW - Na/K-atpase
KW - Protein kinases
KW - Protein phosphatases
KW - Slow afterhyperpolarization
KW - Sodium pump
UR - http://www.scopus.com/inward/record.url?scp=85068161465&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.0265-19.2019
DO - 10.1523/JNEUROSCI.0265-19.2019
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C2 - 31085608
AN - SCOPUS:85068161465
SN - 0270-6474
VL - 39
SP - 5440
EP - 5451
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 28
ER -