Protein kinase C mediates the desensitization of CCh-activated nonselective cationic current in guinea-pig gastric myocytes

1998 ◽  
Vol 436 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Young Chul Kim ◽  
Sung Joon Kim ◽  
Jae Hoon Sim ◽  
Jae Yeoul Jun ◽  
Tong Mook Kang ◽  
...  
2001 ◽  
Vol 441 (4) ◽  
pp. 417-424 ◽  
Author(s):  
Seung Cheol Ahn ◽  
Sang Jin Lee ◽  
Jae Hoon Sim ◽  
Insuk So ◽  
Ki Whan Kim ◽  
...  

1991 ◽  
Vol 56 (3) ◽  
pp. 287-296 ◽  
Author(s):  
Susumu Etoh ◽  
Akemichi Baba ◽  
Heitaroh Iwata

1998 ◽  
Vol 80 (3) ◽  
pp. 1547-1551 ◽  
Author(s):  
Nadav Astman ◽  
Michael J. Gutnick ◽  
Ilya A. Fleidervish

Astman, Nadav, Michael J. Gutnick, and Ilya A. Fleidervish. Activation of protein kinase C increases neuronal excitability by regulating persistent Na+ current in mouse neocortical slices. J. Neurophysiol. 80: 1547–1551, 1998. Effects of the protein kinase C activating phorbol ester, phorbol 12-myristate 13-acetate (PMA), were studied in whole cell recordings from layer V neurons in slices of mouse somatosensory neocortex. PMA was applied intracellularly (100 nM to 1 μM) to restrict its action to the cell under study. In current-clamp recordings, it enhanced neuronal excitability by inducing a 10- to 20-mV decrease in voltage threshold for action-potential generation. Because spike threshold in neocortical neurons critically depends on the properties of persistent Na+ current ( I NaP), effects of PMA on this current were studied in voltage clamp. After blocking K+ and Ca2+ currents, I NaP was revealed by applying slow depolarizing voltage ramps from −70 to 0 mV. Intracellular PMA induced a decrease in I NaP at very depolarized membrane potentials. It also shifted activation of I NaP in the hyperpolarizing direction, however, such that there was a significant increase in persistent inward current at potentials more negative than −45 mV. When tetrodotoxin (TTX) was added to the bath, blocking I NaP and leaving only an outward nonspecific cationic current ( I cat), PMA had no apparent effect on responses to voltage ramps. Thus PMA did not affect I cat, and it did not induce any additional current. Intracellular application of the inactive PMA analogue, 4α-PMA, did not affect I NaP. The specific protein kinase C inhibitors, chelerythrine (20 μM) and calphostin C (10 μM), blocked the effect of PMA on I NaP. The data suggest that PMA enhances neuronal excitability via a protein kinase C–mediated increase in I NaP at functionally critical subthreshold voltages. This novel effect would modulate all neuronal functions that are influenced by I NaP, including synaptic integration and active backpropagation of action potential from the soma into the dendrites.


1993 ◽  
Vol 265 (6) ◽  
pp. C1723-C1728 ◽  
Author(s):  
A. D. Bonev ◽  
M. T. Nelson

We explored the possibility that muscarinic receptor stimulation can inhibit ATP-sensitive K+ (KATP) channels in smooth muscle cells from guinea pig urinary bladder. Whole cell K+ currents were measured in smooth muscle cells isolated from the detrusor muscle of the guinea pig bladder. Stimulation of muscarinic receptors by carbachol (CCh; 10 microM) inhibited KATP currents by 60.7%. Guanosine 5'-O-(2-thiodiphosphate) in the pipette (internal) solution prevented the CCh-induced inhibition of KATP currents. Activators of protein kinase C (PKC), a diacylglycerol analogue, and phorbol 12-myristate 13-acetate inhibited KATP currents by 63.5 and 73.9%, respectively. Blockers of PKC (bisindolylmaleimide GF-109203X and calphostin C) greatly reduced CCh inhibition of KATP currents. We propose that muscarinic receptor stimulation inhibits KATP channels in smooth muscle cells from urinary bladder through activation of PKC.


Pharmacology ◽  
1996 ◽  
Vol 53 (1) ◽  
pp. 60-65 ◽  
Author(s):  
H.S. Odes ◽  
R. Reimer ◽  
R. Muallem ◽  
M. Schwenk ◽  
W. Beil ◽  
...  

1991 ◽  
Vol 56 (3) ◽  
pp. 287-296
Author(s):  
Susumu Etoh ◽  
Akemichi Baba ◽  
Heitaroh lwata

1995 ◽  
Vol 67 ◽  
pp. 206
Author(s):  
Sanae Nakamura ◽  
Tsuyoshi Isliibashi ◽  
Mitsuo Mita ◽  
Takao Hashimoto ◽  
Kazuhiko Oishi ◽  
...  

Neuropeptides ◽  
1996 ◽  
Vol 30 (3) ◽  
pp. 249-260 ◽  
Author(s):  
S Brunelleschi ◽  
S Guidotto ◽  
E Tonso ◽  
I Viano ◽  
R Fantozzi

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