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 differences between endo- and perilymphatic fluids in labyrinthine organs and generates the transepithelial potential. The ensuing electrochemical potential for K sustains the transduction current which regulates activity at the cytoneural junction. Clofilium, a compound which is known to block cardiac K channels and to decrease the endocochlear potential, was applied to the endolymphatic side of the isolated frog semicircular canal. The drug abolished the transepithelial potential and increased 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 reduced the rate of occurrence of miniature excitatory postsynaptic potentials (mEPSPs), both at rest and in response to mechanical stimulation (sinusoidal rotation at 0.1 Hz, 12.5 deg/s2 peak acceleration). This 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 intervals between successive mEPSPs remained exponentially distributed; this suggests a direct effect of clofilium on the postsynaptic membrane, in addition to any possible presynaptic effects. Spike discharge by the afferent fibre was almost completely abolished at rest and responses to mechanical stimulation were reduced by 85-90%. These effects cannot be accounted for by the mild reduction of mEPSP rates and confirm a direct action of clofilium on the afferent postsynaptic terminal.
Rossi
M L
ML
Dipartimento di Biologia, Università di Ferrara, Italy.
Ferrary
E
E
Martini
A
A
Martini
M
M
Pelucchi
B
B
Bernard
C
C
Teixeira
M
M
Sterkers
O
O
Fesce
R
R
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D010812:Physical Stimulation; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D011894:Rana pipiens; D012665:Semicircular Canals / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; C022799:clofilium; D011188:Potassium