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Received June 10, 2004
Revised July 8, 2004
Accepted after revision July 16, 2004
1 Yale University
2 University of Pennsylvania
* To whom correspondence should be addressed. E-mail: dhasakumar.navaratnam{at}yale.edu.
Abstract Electrical resonance is a mechanism used by birds and many vertebrates to discriminate between frequencies of sound, and occurs when the intrinsic oscillation in the membrane potential of a specific hair cell corresponds to a specific stimulus sound frequency. This intrinsic oscillation results from an interplay between an inward Ca2+ current and the resultant activation of a hyperpolarizing Ca2+ activated K+ current. These channels are predicted to lie in close proximity owing to the fast oscillation in membrane potential. The interplay of these channels is widespread in the nervous system, where they perform numerous roles including the control of synaptic release, burst frequency and circadian rhythm generation. Here, we used confocal microscopy, to show that these two ion channels are clustered and co-localized in the chick hair cell membrane. The majority of Ca2+ channels were co-localized while the proportion of co-localized BK channels was markedly less. In addition, we report both an apical-basal gradient of these clusters in individual hair cells, as well as a gradient in the number of clusters between hair cells along the tonotopic axis. These results give physical confirmation of previous predictions. Since the proportion of co-localized channels was a constant function of Ca2+ channels (and not of BK channels), these results suggest that their co-localization is determined by the former. The molecular underpinnings to their clustering and co-localization are likely common to that in other neuronal cells.
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