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Local response of L‐type Ca 2+ current to nitric oxide in frog ventricular myocytes
Author(s) -
Dittrich Michael,
Jurevičius Jonas,
Georget Marie,
Rochais Francesca,
Fleischmann Bernd Kurt,
Hescheler Jürgen,
Fischmeister Rodolphe
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.00109.x
Subject(s) - sodium nitroprusside , snap , nitric oxide , forskolin , chemistry , isoprenaline , medicine , soluble guanylyl cyclase , biophysics , stimulation , endocrinology , biology , cyclic gmp , computer graphics (images) , computer science , organic chemistry
1 The regulation of L‐type Ca 2+ current ( I Ca ) by the two nitric oxide (NO) donors sodium nitroprusside (SNP, 1 μ m to 1 m m ) and (±)‐ S‐ nitroso‐ N‐ acetylpenicillamine (SNAP, 3 or 10 μ m ) was investigated in frog ventricular myocytes using double voltage clamp and double‐barrelled microperfusion techniques. 2 SNP and SNAP depressed the isoprenaline (ISO, 10‐100 n m )‐ or forskolin (FSK, 1 μ m )‐mediated stimulation of I Ca via cGMP activation of the cGMP‐stimulated phosphodiesterase (PDE2). Complete inhibition of the ISO (100 n m ) response was observed at 1 m m SNP. 3 When SNP was applied locally, i.e. to one‐half of the cell, and ISO to the whole cell, the response of I Ca to ISO was strongly antagonized in the cell half exposed to SNP (up to 100 % inhibition at 1 m m SNP) but a relatively small depression was observed in the other half of the cell (only 20 % inhibition at 1 m m SNP). 4 The NO scavenger 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl 3‐oxide (carboxy‐PTIO, 1 m m ) reversed the local effect of SNAP (3 μ m ) on FSK‐stimulated I Ca when applied to the same side as the NO donor, but had no effect when applied to the other side of the cell. 5 A local application of erythro ‐9‐(2‐hydroxy‐3‐nonyl)adenine (EHNA, 30 μ m ), a selective inhibitor of PDE2, fully reversed the local effect of SNP (100 μ m ) or SNAP (10 μ m ) on I Ca but had no effect on the distant response. 6 When EHNA was applied on the distant side, with SNP (1 m m ) and ISO (100 n m ) applied locally, the distant effect of SNP was fully reversed. 7 Our results demonstrate that in frog ventricular myocytes stimulation of guanylyl cyclase by NO leads to a strong local depletion of cAMP near the L‐type Ca 2+ channels due to activation of PDE2, but only to a modest reduction of cAMP in the rest of the cell. This may be explained by the existence of a tight microdomain between L‐type Ca 2+ channels and PDE2.