title: Rectification of rabbit cardiac ryanodine receptor current by endogenous polyamines.
abstract: The actions of three endogenous polyamines (spermine, spermidine, and putrescine) were defined on Ca2+ release channels (ryanodine receptors, RyRs) isolated from rabbit cardiac sarcoplasmic reticulum. The current-voltage relationship of the RyR channel was N-shaped in the presence of polyamine (1-5 mM). Polyamine blocked conduction near 0 mV, but the blockade was relieved at large potentials. Polyamines acted (blocked) from both sides of the channel. Polyamine efficacy was dependent on current direction and was inversely related to the ion selectivity of the RyR pore. This suggests that polyamine interacts with current-carrying ions in the permeation pathway. The apparent half-block concentration of spermine at 0 mV was < 0.1 mM. The features of polyamine blockade suggest that the polyamines are permeable cationic blockers of the RyR channel. Further, the levels of polyamines found in muscle cells are sufficient to block single RyR channels and thus may alter the sarcoplasmic reticulum Ca2+ release process in situ.
authors.affiliation: Department of Physiology, Loyola University Chicago, Maywood, Illinois 60153, USA.
authors.forename: A
authors.initials: A
authors.lastname: Uehara
authors.forename: M
authors.initials: M
authors.lastname: Fill
authors.forename: P
authors.initials: P
authors.lastname: Vélez
authors.forename: M
authors.initials: M
authors.lastname: Yasukochi
authors.forename: I
authors.initials: I
authors.lastname: Imanaga
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004553:Electric Conductivity; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles; D015640:Ion Channel Gating / Q000187:drug effects; D008051:Lipid Bilayers; D008564:Membrane Potentials / Q000187:drug effects; D009124:Muscle Proteins / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D011700:Putrescine / Q000494:pharmacology* / Q000502:physiology; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D013095:Spermidine / Q000494:pharmacology* / Q000502:physiology; D013096:Spermine / Q000494:pharmacology* / Q000502:physiology
chemical_list: D015220:Calcium Channels; D008051:Lipid Bilayers; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D013096:Spermine; D013095:Spermidine; D011700:Putrescine