Modeling hair cell tuning by expression gradients of potassium channel beta subunits.
The receptor potential of sensory hair cells arises from the gating of mechanosensitive cation channels, but its amplitude and time course also depend on the number and kinetics of voltage-gated ion channels in each cell. Prominent among these are "BK" potassium channels encoded by the slo gene that support electrical tuning in some hair cells. Hair cells tuned to low frequencies have slowly gating BK channels, whereas those of higher-frequency hair cells gate more rapidly. Alternative splicing of the slo gene mRNA that encodes the pore-forming alpha subunit can alter BK channel kinetics, and gating is dramatically slowed by coexpression with modulatory beta subunits. The effect of the beta subunit is consistent with low-frequency tuning, and beta mRNA is expressed at highest levels in the low frequency apex of the bird's auditory epithelium. How might an expression gradient of beta subunits contribute to hair cell tuning? The present work uses a computational model of hair cell-tuning based on the functional properties of BK channels expressed from hair cell alpha and beta slo cDNA. The model reveals that a limited tonotopic gradient could be achieved simply by altering the fraction of BK channels in each hair cell that are combined with beta subunits. However, complete coverage of the tuning spectrum requires kinetic variants in addition to those modeled here.
Ramanathan
Krishnan
K
The Center for Hearing and Balance, Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2195 USA.
Fuchs
Paul A
PA
D000494:Allosteric Regulation; D000818:Animals; D002460:Cell Line; D002645:Chickens; D003001:Cloning, Molecular; D004594:Electrophysiology / Q000379:methods; D005091:Exons; D014644:Genetic Variation; D006198:Hair Cells, Auditory / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D007700:Kinetics; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008954:Models, Biological; D024681:Potassium Channels, Calcium-Activated / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D011994:Recombinant Proteins