NIFLUMIC ACID DIFFERENTIALLY MODULATES 2 TYPES OF SKELETAL RYANODINE-SENSITIVE CA2-RELEASE CHANNELS()

The effects of niflumic acid on ryanodine receptors (RyRs) of frog ske letal muscle were studied by incorporating sarcoplasmic reticulum (SR) vesicles into planar lipid bilayers. Frog muscle had two distinct typ es of RyRs in the SR: one showed a bell-shaped channel activation curv e against cytoplasmic Ca2+ or niflumic acid, and its mean open probabi lity (P-o) was increased by perchlorate at 20-30 mM (termed ''alpha-li ke'' RyR); the other showed a sigmoidal activation curve against Ca2or niflumic acid, with no effect on perchlorate (termed ''beta-like'' RyR). The unitary conductance and reversal potential of both channel t ypes were unaffected after exposure to niflumic acid when clamped at 0 mV. When clamped at more positive potentials, the beta-like RyR chann el rectified this, increasing the unitary current. Treatment with nifl umic acid did not inhibit the response of both channels to Ca2+ releas e channel modulators such as caffeine, ryanodine, and ruthenium red. T he different effects of niflumic acid on P-o and the unitary current a mplitude in both types of channels may be attributable to the lack or the presence of inactivation sites and/or distinct responses to agonis ts.