THE EFFECT OF CLOFILIUM, A K-CHANNEL BLOCKER, ON THE ELECTROGENIC K SECRETION AND THE SENSORY DISCHARGE AT THE FROG SEMICIRCULAR CANAL

Potassium transport by dark cells produces marked K-concentration diff erences between endo- and perilymphatic fluids in labyrinthine organs and generates the transepithelial potential. The ensuing electrochemic al potential for K sustains the transduction current which regulates a ctivity at the cytoneural junction. Clofilium, a compound which is kno wn to block cardiac K channels and to decrease the endocochlear potent ial, was applied to the endolymphatic side of the isolated from semici rcular canal. The drug abolished the transepithelial potential and inc reased K outflux from the lumen to the dark cells (or the basolateral perilymph) with no apparent interference with active K secretion. When applied to the perilymphatic side in the intact labyrinth clofilium r educed the rate of occurrence of miniature excitatory postsynaptic pot entials (mEPSPs), both at rest and in response to mechanical stimulati on (sinusoidal rotation at 0.1 Hz, 12.5 deg/s(2) peak acceleration). T his effect may be related to a reduced K-electrochemical unbalance and a decreased transduction current. The drug consistently reduced mEPSP size, although amplitude distributions remained log-normal and time i ntervals between successive mEPSPs remained exponentially distributed; this suggests a direct effect of clofilium on the postsynaptic membra ne, in addition to any possible presynaptic effects. Spike discharge b y the afferent fibre was almost completely abolished at rest and respo nses to mechanical stimulation were reduced by 85-90%. These effects c annot be accounted for by the mild reduction of mEPSP rates and confir m a direct action of clofilium on the afferent postsynaptic terminal.