RESUMO
Tip links between adjacent stereocilia are believed to gate mechano-electrical transducer (MET) channels and mediate the electrical responses of sensory hair cells. We found that mouse auditory hair cells that lack tip links due to genetic mutations or exposure to the Ca(2+) chelator BAPTA can, however, still respond to mechanical stimuli. These MET currents have unusual properties and are predominantly of the opposite polarity relative to those measured when tip links are present. There are other striking differences, for example, the channels are usually all closed when the hair cell is not stimulated and the currents in response to strong stimuli can be substantially larger than normal. These anomalous MET currents can also be elicited early in development, before the onset of mechano-electrical transduction with normal response polarity. Current-voltage curves of the anomalous MET currents are linear and do not show the rectification characteristic of normal MET currents. The permeant MET channel blocker dihydrostreptomycin is two orders of magnitude less effective in blocking the anomalous MET currents. The findings suggest the presence of a large population of MET channels with pore properties that are distinct from those of normal MET channels. These channels are not gated by hair-bundle links and can be activated under a variety of conditions in which normal tip-link-mediated transduction is not operational.
Assuntos
Permeabilidade da Membrana Celular/fisiologia , Células Ciliadas Auditivas/fisiologia , Canais Iônicos/fisiologia , Mecanotransdução Celular/fisiologia , Animais , Animais Recém-Nascidos , Proteínas Relacionadas a Caderinas , Caderinas/genética , Permeabilidade da Membrana Celular/genética , Quelantes/farmacologia , Sulfato de Di-Hidroestreptomicina/farmacologia , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Embrião de Mamíferos , Feminino , Células Ciliadas Auditivas/citologia , Células Ciliadas Auditivas/efeitos dos fármacos , Técnicas In Vitro , Canais Iônicos/efeitos dos fármacos , Masculino , Mecanotransdução Celular/efeitos dos fármacos , Mecanotransdução Celular/genética , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Miosina VIIa , Miosinas/genética , Órgão Espiral/citologia , Precursores de Proteínas/genéticaRESUMO
Transient receptor potential channels have diverse roles in mechanosensation. Evidence is accumulating that members of the canonical subfamily of TRP channels (TRPC) are involved in touch and hearing. Characteristic features of TRP channels include their high structural homology and their propensity to form heteromeric complexes which suggests potential functional redundancy. We previously showed that TRPC3 and TRPC6 double knockout animals have deficits in light touch and hearing whilst single knockouts were apparently normal. We have extended these studies to analyse deficits in global quadruple TRPC1, 3, 5 and 6 null mutant mice. We examined both touch and hearing in behavioural and electrophysiological assays, and provide evidence that the quadruple knockout mice have larger deficits than the TRPC3 TRPC6 double knockouts. Mechano-electrical transducer currents of cochlear outer hair cells were however normal. This suggests that TRPC1, TRPC3, TRPC5 and TRPC6 channels contribute to cutaneous and auditory mechanosensation in a combinatorial manner, but have no direct role in cochlear mechanotransduction.
Assuntos
Audição/fisiologia , Canais de Cátion TRPC/fisiologia , Tato/fisiologia , Animais , Potenciais Evocados Auditivos do Tronco Encefálico , Células Ciliadas Auditivas/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Canais de Cátion TRPC/genética , Canal de Cátion TRPC6 , Testes de Função VestibularRESUMO
Inflammation due to bacterial infection exacerbates hearing loss caused by aminoglycoside antibiotic treatment in a mouse model of sepsis (Koo et al.).