PMID- 10482769
OWN - NLM
STAT- MEDLINE
DCOM- 19991101
LR  - 20171213
IS  - 0022-3077 (Print)
IS  - 0022-3077 (Linking)
VI  - 82
IP  - 3
DP  - 1999 Sep
TI  - Angiotensin II decreases neuronal delayed rectifier potassium current: role of 
      calcium/calmodulin-dependent protein kinase II.
PG  - 1560-8
AB  - Angiotensin II (Ang II) acts at specific receptors located on neurons in the 
      hypothalamus and brain stem to elicit alterations in blood pressure, fluid 
      intake, and hormone secretion. These actions of Ang II are mediated via Ang II 
      type 1 (AT1) receptors and involve modulation of membrane ionic currents and 
      neuronal activity. In previous studies we utilized neurons cultured from the 
      hypothalamus and brain stem of newborn rats to investigate the AT1 
      receptor-mediated effects of Ang II on neuronal K+ currents. Our data indicate 
      that Ang II decreases neuronal delayed rectifier (Kv) current, and that this 
      effect is partially due to activation of protein kinase C (PKC), specifically 
      PKCalpha. However, the data also indicated that another Ca2+-dependent mechanism 
      was also involved in addition to PKC. Because Ca2+/calmodulin-dependent protein 
      kinase II (CaM KII) is a known modulator of K+ currents in neurons, we 
      investigated the role of this enzyme in the AT1 receptor-mediated reduction of 
      neuronal Kv current by Ang II. The reduction of neuronal Kv current by Ang II was 
      attenuated by selective inhibition of either calmodulin or CaM KII and was 
      mimicked by intracellular application of activated (autothiophosphorylated) CaM 
      KIIalpha. Concurrent inhibition of CaM KII and PKC completely abolished the 
      reduction of neuronal Kv by Ang II. Consistent with these findings is the 
      demonstration that Ang II increases CaM KII activity in neuronal cultures, as 
      evidenced by increased levels of autophosphorylated CaM KIIalpha subunit. Last, 
      single-cell reverse transcriptase (RT)-PCR analysis revealed the presence of AT1 
      receptor-, CaM KIIalpha-, and PKCalpha subunit mRNAs in neurons that responded to 
      Ang II with a decrease in Kv current. The present data indicate that the AT1 
      receptor-mediated reduction of neuronal Kv current by Ang II involves a 
      Ca2+/calmodulin/CaM KII pathway, in addition to the previously documented 
      involvement of PKC.
FAU - Zhu, M
AU  - Zhu M
AD  - Department of Physiology, College of Medicine, and University of Florida Brain 
      Institute, University of Florida, Gainesville, Florida 32610, USA.
FAU - Gelband, C H
AU  - Gelband CH
FAU - Posner, P
AU  - Posner P
FAU - Sumners, C
AU  - Sumners C
LA  - eng
GR  - HL-49130/HL/NHLBI NIH HHS/United States
GR  - NS-19441/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurophysiol
JT  - Journal of neurophysiology
JID - 0375404
RN  - 0 (Calmodulin)
RN  - 0 (Delayed Rectifier Potassium Channels)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Receptor, Angiotensin, Type 2)
RN  - 0 (Receptors, Angiotensin)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
SB  - IM
MH  - Angiotensin II/pharmacology/*physiology
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2
MH  - Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/*physiology
MH  - Calmodulin/antagonists & inhibitors
MH  - Delayed Rectifier Potassium Channels
MH  - Electric Conductivity
MH  - Enzyme Activation/physiology
MH  - Neurons/*metabolism
MH  - Potassium Channel Blockers
MH  - Potassium Channels/*drug effects/*physiology
MH  - *Potassium Channels, Voltage-Gated
MH  - Protein Kinase C/antagonists & inhibitors/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Angiotensin, Type 1
MH  - Receptor, Angiotensin, Type 2
MH  - Receptors, Angiotensin/physiology
EDAT- 1999/09/14 00:00
MHDA- 1999/09/14 00:01
CRDT- 1999/09/14 00:00
PHST- 1999/09/14 00:00 [pubmed]
PHST- 1999/09/14 00:01 [medline]
PHST- 1999/09/14 00:00 [entrez]
AID - 10.1152/jn.1999.82.3.1560 [doi]
PST - ppublish
SO  - J Neurophysiol. 1999 Sep;82(3):1560-8. doi: 10.1152/jn.1999.82.3.1560.