Coupling between L-type Ca$^2+$ channels (dihydropyridine receptors,
DHPRs) and ryanodine receptors (RyRs) plays a pivotal role in excitation-contraction
(E-C) coupling in cardiac myocytes, and Ca$^2+$ influx is generally
accepted as the trigger of sarcoplasmic reticulum (SR) Ca$^2+$
release. The L-type Ca$^2+$ channel agonist BayK 8644 (BayK)
has also been reported to alter RyR gating via a functional linkage
between DHPR and RyR, independent of Ca$^2+$ influx. Here, the
effect of rapid BayK application on resting RyR gating in intact
ferret ventricular myocytes was measured as Ca$^2+$ spark frequency
(CaSpF) by confocal microscopy and fluo 3. BayK increased resting
CaSpF by 401+/-15\% within 10 seconds in Ca$^2+$-free solution,
and depolarization had no additional effect. The effect of BayK on
CaSpF was dose-dependent, but even 50 nmol/L BayK induced a rapid
245+/-12\% increase in CaSpF. Nifedipine (5 micromol/L) had no effect
by itself on CaSpF, but it abolished the BayK effect (presumably
by competitive inhibition at the DHPR). The nondihydropyridine Ca$^2+$
channel agonist FPL-64176 (1 micromol/L) did not alter CaSpF (despite
rapid and potent enhancement of Ca$^2+$ current, I(Ca)). In striking
contrast to the very rapid and depolarization-independent effect
of BayK on CaSpF, BayK increased I(Ca) only slowly (tau=18 seconds),
and the effect was greatly accelerated by depolarization. We conclude
that in ferret ventricular myocytes, BayK effects on I(Ca) and CaSpF
both require drug binding to the DHPR, but postreceptor pathways
may diverge in transmission to the gating of the L-type Ca$^2+$
channel and RyR.
%0 Journal Article
%1 Kato_2000_106
%A Katoh, H.
%A Schlotthauer, K.
%A Bers, D. M.
%D 2000
%J Circ. Res.
%K 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, 10903993 3-Pyridinecarboxylic Acid, Action Agonists, Animals, Blockers, C, Caffeine, Calcium Calcium, Cations, Cells, Channel Channel, Channels, Chlorides, Confocal, Cross-Talk, Cultured, Electric Ferrets, Gating, Gov't, Heart Heart, Ion L-Type, Membrane Methyl Microscopy, Myocardium, Nifedipine, Niflumic Non-U.S. P.H.S., Patch-Clamp Potentials, Pyrroles, Rabbits, Receptor Release Research Reticulum, Ryanodine Sarcoplasmic Sodium, Stimulation, Support, Techniques, U.S. Ventricles, acid, alcium ester,
%N 2
%P 106--111
%T Transmission of information from cardiac dihydropyridine receptor
to ryanodine receptor: evidence from BayK 8644 effects on resting
Ca$^2+$ sparks.
%U http://circres.ahajournals.org/cgi/content/full/87/2/106
%V 87
%X Coupling between L-type Ca$^2+$ channels (dihydropyridine receptors,
DHPRs) and ryanodine receptors (RyRs) plays a pivotal role in excitation-contraction
(E-C) coupling in cardiac myocytes, and Ca$^2+$ influx is generally
accepted as the trigger of sarcoplasmic reticulum (SR) Ca$^2+$
release. The L-type Ca$^2+$ channel agonist BayK 8644 (BayK)
has also been reported to alter RyR gating via a functional linkage
between DHPR and RyR, independent of Ca$^2+$ influx. Here, the
effect of rapid BayK application on resting RyR gating in intact
ferret ventricular myocytes was measured as Ca$^2+$ spark frequency
(CaSpF) by confocal microscopy and fluo 3. BayK increased resting
CaSpF by 401+/-15\% within 10 seconds in Ca$^2+$-free solution,
and depolarization had no additional effect. The effect of BayK on
CaSpF was dose-dependent, but even 50 nmol/L BayK induced a rapid
245+/-12\% increase in CaSpF. Nifedipine (5 micromol/L) had no effect
by itself on CaSpF, but it abolished the BayK effect (presumably
by competitive inhibition at the DHPR). The nondihydropyridine Ca$^2+$
channel agonist FPL-64176 (1 micromol/L) did not alter CaSpF (despite
rapid and potent enhancement of Ca$^2+$ current, I(Ca)). In striking
contrast to the very rapid and depolarization-independent effect
of BayK on CaSpF, BayK increased I(Ca) only slowly (tau=18 seconds),
and the effect was greatly accelerated by depolarization. We conclude
that in ferret ventricular myocytes, BayK effects on I(Ca) and CaSpF
both require drug binding to the DHPR, but postreceptor pathways
may diverge in transmission to the gating of the L-type Ca$^2+$
channel and RyR.
@article{Kato_2000_106,
abstract = {Coupling between L-type {C}a$^{2+}$ channels (dihydropyridine receptors,
DHPRs) and ryanodine receptors (RyRs) plays a pivotal role in excitation-contraction
(E-C) coupling in cardiac myocytes, and {C}a$^{2+}$ influx is generally
accepted as the trigger of sarcoplasmic reticulum (SR) {C}a$^{2+}$
release. The L-type {C}a$^{2+}$ channel agonist BayK 8644 (BayK)
has also been reported to alter RyR gating via a functional linkage
between DHPR and RyR, independent of {C}a$^{2+}$ influx. Here, the
effect of rapid BayK application on resting RyR gating in intact
ferret ventricular myocytes was measured as {C}a$^{2+}$ spark frequency
(CaSpF) by confocal microscopy and fluo 3. BayK increased resting
CaSpF by 401+/-15\% within 10 seconds in {C}a$^{2+}$-free solution,
and depolarization had no additional effect. The effect of BayK on
CaSpF was dose-dependent, but even 50 nmol/L BayK induced a rapid
245+/-12\% increase in CaSpF. Nifedipine (5 micromol/L) had no effect
by itself on CaSpF, but it abolished the BayK effect (presumably
by competitive inhibition at the DHPR). The nondihydropyridine {C}a$^{2+}$
channel agonist FPL-64176 (1 micromol/L) did not alter CaSpF (despite
rapid and potent enhancement of {C}a$^{2+}$ current, I(Ca)). In striking
contrast to the very rapid and depolarization-independent effect
of BayK on CaSpF, BayK increased I(Ca) only slowly (tau=18 seconds),
and the effect was greatly accelerated by depolarization. We conclude
that in ferret ventricular myocytes, BayK effects on I(Ca) and CaSpF
both require drug binding to the DHPR, but postreceptor pathways
may diverge in transmission to the gating of the L-type {C}a$^{2+}$
channel and RyR.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Katoh, H. and Schlotthauer, K. and Bers, D. M.},
biburl = {https://www.bibsonomy.org/bibtex/236e19115bbde7a4c81fd97ce3bedd597/hake},
description = {The whole bibliography file I use.},
file = {Kato_2000_106.pdf:Kato_2000_106.pdf:PDF},
interhash = {b1354778c84947159bf420b7fb8e1170},
intrahash = {36e19115bbde7a4c81fd97ce3bedd597},
journal = {Circ. Res.},
key = 291,
keywords = {1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, 10903993 3-Pyridinecarboxylic Acid, Action Agonists, Animals, Blockers, C, Caffeine, Calcium Calcium, Cations, Cells, Channel Channel, Channels, Chlorides, Confocal, Cross-Talk, Cultured, Electric Ferrets, Gating, Gov't, Heart Heart, Ion L-Type, Membrane Methyl Microscopy, Myocardium, Nifedipine, Niflumic Non-U.S. P.H.S., Patch-Clamp Potentials, Pyrroles, Rabbits, Receptor Release Research Reticulum, Ryanodine Sarcoplasmic Sodium, Stimulation, Support, Techniques, U.S. Ventricles, acid, alcium ester,},
month = Jul,
number = 2,
pages = {106--111},
pmid = {10903993},
timestamp = {2009-06-03T11:21:17.000+0200},
title = {Transmission of information from cardiac dihydropyridine receptor
to ryanodine receptor: evidence from BayK 8644 effects on resting
{C}a$^{2+}$ sparks.},
url = {http://circres.ahajournals.org/cgi/content/full/87/2/106},
volume = 87,
year = 2000
}