The fast activating potassium current, I(K,f), in guinea-pig inner hair cells is regulated by protein kinase A.
The mammalian inner hair cell (IHC) responds to displacements produced in the cochlea by sound by releasing neurotransmitter from its basal pole. A basolateral fast activating potassium current, called I(K,f), allows IHCs to act as sensory cells at high frequencies by shortening the membrane time constant. This current is co-expressed with a slower activating current, I(K,s). We have studied the intracellular regulation of IHC currents using the whole-cell patch clamp technique in conjunction with agents that influence the function of protein kinase A (PKA). Bath applied 8-Bromo-cAMP, an activator of PKA, increased the amplitude of outwardly rectifying currents and shortened the exponential time constant of activation. Following blockade of I(K,s) by intracellular 4-AP, I(K,f) could be reduced in amplitude by H-89, an inhibitor of PKA. Our results suggest that PKA regulates I(K,f) and so shapes the frequency response of IHCs.
Jagger
D J
DJ
Department of Physiology, University College London, UK.
Ashmore
J F
JF
D015761:4-Aminopyridine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D013449:Sulfonamides
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D015221:Potassium Channels; D013449:Sulfonamides; D015124:8-Bromo Cyclic Adenosine Monophosphate; D004533:Egtazic Acid; D015761:4-Aminopyridine; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide