Niflumic acid differentially modulates two types of skeletal ryanodine-sensitive Ca2+-release channels

The effects of niflumic acid on ryanodinereceptors (RyRs) of frog skeletal muscle were studied by incorporatingsarcoplasmic reticulum (SR) vesicles into planar lipid bilayers. Frogmuscle had two distinct types of RyRs in the SR: one showed abell-shaped channel activation curve against cytoplasmicCa²⁺ or niflumic acid, and its mean open probability(P_o) was increased by perchlorate at 20-30mM (termed "-like" RyR); the other showed a sigmoidalactivation curve against Ca²⁺ or niflumic acid, with noeffect on perchlorate (termed "-like" RyR). The unitaryconductance and reversal potential of both channel types wereunaffected after exposure to niflumic acid when clamped at 0 mV. Whenclamped at more positive potentials, the -like RyRchannel rectified this, increasing the unitary current. Treatment withniflumic acid did not inhibit the response of both channels toCa²⁺ release channel modulators such as caffeine,ryanodine, and ruthenium red. The different effects of niflumic acid onP_o and the unitary current amplitude in both typesof channels may be attributable to the lack or the presence ofinactivation sites and/or distinct responses to agonists.