Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 7660679

Cardioprotective drugs decrease the Na+ background current.

S R Park·G H Ryu·C K Suh
View original source ↗Export metadata ↓

Abstract

Cardiac dysfunctions such as myocardial functional failure and ventricular arrhythmia have been largely attributed to intracellular Ca2+ overload. One of the mechanisms of intracellular Ca2+ overload involves a rapid influx of Ca2+ via Na(+)-Ca2+ exchange during the reperfusion which utilizes the accumulation of Na+ in myocytes during ischemic cardiac arrest. Possible sources of the intracellular Na+ accumulation include Na+ channel, Na(+)-H+ exchange, Na(+)-Ca2+ exchange, and Na+ background current. In this study, we studied the role of the Na+ background current in intracellular Na+ accumulation during the cardiac arrest by measuring the Na+ background current in guinea pig ventricular myocytes with whole cell clamp method and evaluating the effects of cardioprotective drugs on the Na+ background current. The results were as follows: (1) The Na+ background inward current at -40 mV membrane potential was larger at Ca2+ free solution than 1.8 mM Ca2+ solution. (2) The Na+ background current was not affected by verapamil. (3) 2 microM O-(N, N-hexamethylene)-amiloride (HMA) decreased the Na+ background current at negative membrane potential. (4) The new cardioprotective drug, R 56865, decreased the Na+ background current. These results suggest that the Na+ background current plays a role in increasing the intracellular Na+ activity during high K+ cardioplegia and the blocking effect of myoprotective drugs, such as R 56865, on the Na+ background current may contribute to myocardial protection after cardioplegia.

Explore related subjects

AmilorideAnimalsBenzothiazolesGuinea PigsHeartHeart Arrest, InducedMyocardiumPiperidinesPotassiumSodiumThiazolesVerapamilJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

S R Park, G H Ryu, C K Suh. 1995. Cardioprotective drugs decrease the Na+ background current.. https://doi.org/10.3349/ymj.1995.36.3.278

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed1995

Cloning of the amiloride-sensitive FMRFamide peptide-gated sodium channel.

The peptide Phe-Met-Arg-Phe-NH2 (FMRFamide) and structurally related peptides are present both in invertebrate and vertebrate nervous systems. Although they constitute a major class of invertebrate peptide neurotransmitters, the molecular structure of their receptors has not yet been identified. In neurons of the snail Helix aspersa, as well as in Aplysia bursting and motor neurons, FMRFamide induces a fast excitatory depolarizing response due to direct activation of an amiloride-sensitive Na+ channel. We have now isolated a complementary DNA from Helix nervous tissue; when expressed in Xenopus oocytes, it encodes an FMRFamide-activated Na+ channel (FaNaCh) that can be blocked by amiloride. The corresponding protein shares a very low sequence identity with the previously cloned epithelial Na+ channel subunits and Caenorhabditis elegans degenerins, but it displays the same overall structural organization. To our knowledge, this is the first characterization of a peptide-gated ionotropic receptor.

Amiloride↗
PubMed1995

pH modulates cAMP-induced increase in Na+ transport across frog skin epithelium.

Apical membrane potential (Va), fractional apical membrane resistance (FRa), and/or intracellular pH (pHi) were measured in principal cells of isolated frog (Rana pipiens) skin with microelectrodes under short-circuit conditions. Apical exposure to 0.33 mM 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate (cAMP) depolarized Va, decreased FRa and increased short-circuit current (Isc). cAMP-induced 50% larger effects on Va and Isc at external pH (pHo) of 8.0 than at pHo 6.4. Increasing pHo from 6.4 to 8.0 in presence of cAMP further depolarized Va and increased Isc. cAMP-induced effects on Va and Isc were observed in the absence of Cl- and HCO3- and in the presence of 1 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) or 10 microM 5-(N-ethyl-N-isopropyl)amiloride (EIPA) or 1 microM 5-(N-methyl-N-isobutyl)amiloride (MIA). These data indicate that Na(+)-H+ exchange, Cl(-)-HCO3- exchange, and electrogenic Na(+)-(HCO3-)n cotransport are not involved in cAMP-induced increase in Isc. Apical exposure to 2 mM Cd2+ or Zn2+ depolarized Va, decreased FRa, increased Isc and increased pHi. In HCO(3-)-free solutions containing DIDS, unilateral replacement of apical Cl- by NO3- induced a fast transient depolarization of Va and an increase in Isc. These data suggest that potential-dependent changes in pHi are involved in increases in Isc. However, when changes in Va were minimized by pretreating the basolateral membrane with 25 or 75 mM K+, the cAMP-induced increase in Isc was not blocked. These data indicate that changes in pHi do not play a strict regulatory role but are only permissive in cAMP-induced effects on Isc.

Amiloride↗
PubMed1995

Molecular cloning and functional expression of a novel amiloride-sensitive Na+ channel.

We have isolated a cDNA for a novel human amiloride-sensitive Na+ channel isoform (called delta) which is expressed mainly in brain, pancreas, testis, and ovary. When expressed in Xenopus oocytes, it generates an amiloride-sensitive Na+ channel with biophysical and pharmacological properties distinct from those of the epithelial Na+ channel, a multimeric assembly of alpha, beta, and gamma subunits. The Na+ current produced by the new delta isoform is increased by two orders of magnitude after coexpression of the beta and gamma subunit of the epithelial Na+ channel showing that delta can associate with other subunits and is part of a novel multisubunit ion channel.

Amiloride↗