RESUMEN
Spontaneous rhythmic activity of pacemaker neurons in the central nervous system underlies fundamental neurological processes such as locomotion, cognition and circadian rhythm. Among the wide range of ion channels required for its generation, the Ca2+-activated K+(KCa) channels play a prominent role in maintaining physiologically-relevant frequency and pattern of pacemaker activity. Much of our understanding of the functions of KCa channels in pacemaker neurons have been derived from pharmacological studies using channel modulators, such as iberiotoxin and apamin. Despite the significant advances made, recent studies have painted an increasingly complex picture of the effects of widely used KCa channel modulators on unintended targets that may confound our under?standing of their functions. In this review, we discussed the utility and shortcomings of the KCa channel modulators, and highlighted the significance of these findings, because the KCa channel modulators have been used in early clinical trials to treat disorders ranging from Parkinson disease to alcoholism.
RESUMEN
Previously, we reported that besides retinal ganglion cell (RGC) spike, there is ~ 10 Hz oscillatory rhythmic activity in local field potential (LFP) in retinal degeneration model, rd1 mice. The more recently identified rd10 mice have a later onset and slower rate of photoreceptor degeneration than the rd1 mice, providing more therapeutic potential. In this study, before adapting rd10 mice as a new animal model for our electrical stimulation study, we investigated electrical characteristics of rd10 mice. From the raw waveform of recording using 8x8 microelectrode array (MEA) from in vitro-whole mount retina, RGC spikes and LFP were isolated by using different filter setting. Fourier transform was performed for detection of frequency of bursting RGC spikes and oscillatory field potential (OFP). In rd1 mice, ~10 Hz rhythmic burst of spontaneous RGC spikes is always phase-locked with the OFP and this phase-locking property is preserved regardless of postnatal ages. However, in rd10 mice, there is a strong phase-locking tendency between the spectral peak of bursting RGC spikes (~5 Hz) and the first peak of OFP (~5 Hz) across different age groups. But this phase-locking property is not robust as in rd1 retina, but maintains for a few seconds. Since rd1 and rd10 retina show phase-locking property at different frequency (~10 Hz vs. ~5 Hz), we expect different response patterns to electrical stimulus between rd1 and rd10 retina. Therefore, to extract optimal stimulation parameters in rd10 retina, first we might define selection criteria for responding rd10 ganglion cells to electrical stimulus.