title: Modulation of the Ca(2+) release channel of sarcoplasmic reticulum by amiloride analogs.
abstract: Dichlorobenzamil, phenamil and other amiloride analogs (1-100 microM) elicit transient tension in rabbit skinned muscle fibers. Tension requires preloading of Ca(2+) into the sarcoplasmic reticulum, is facilitated by low-[Mg(2+)] solutions, abolished by ruthenium red or by functional disruption of the sarcoplasmic reticulum, and is followed by inhibition of the caffeine-evoked tension. Bilayer recording of Cs(+) currents through the sarcoplasmic reticulum Ca(2+) release channel reveals that phenamil (10-100 microM) increases the open channel probability, whereas dichlorobenzamil affects the channel activity in a complex concentration- and time-dependent manner: stimulation occurs throughout exposure to 10 microM, but is followed by channel blockade when 100 microM dichlorobenzamil is used. It is concluded that stimulation of the sarcoplasmic reticulum Ca(2+) release channel accounts for the dichlorobenzamil- or phenamil-induced tension in skinned fibers, whereas depletion of sarcoplasmic reticulum Ca(2+) stores and channel block (with dichlorobenzamil) explains the inhibition of the caffeine-evoked tension by amiloride analogs.
authors.affiliation: Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: C G
authors.initials: CG
authors.lastname: Ponte
authors.forename: R C
authors.initials: RC
authors.lastname: Estrela
authors.forename: G
authors.initials: G
authors.lastname: Suarez-Kurtz
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects*; D002592:Cetomacrogol / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology*; D004594:Electrophysiology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008274:Magnesium / Q000502:physiology; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011817:Rabbits; D012430:Ruthenium Red / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects; D012996:Solutions
chemical_list: D015220:Calcium Channels; D004232:Diuretics; D010726:Phosphodiesterase Inhibitors; D019837:Ryanodine Receptor Calcium Release Channel; D015222:Sodium Channels; D012996:Solutions; D012430:Ruthenium Red; C041470:3',4'-dichlorobenzamil; C047088:phenylamil; D002110:Caffeine; D000584:Amiloride; D002592:Cetomacrogol; D008274:Magnesium; D002118:Calcium