Profound alterations in the intrinsic excitability of cerebellar Purkinje neurons following neurotoxin 3-acetylpyridine (3-AP)-induced ataxia in rat: new insights into the role of small conductance K+ channels.
Alterations in the intrinsic properties of Purkinje cells (PCs) may contribute to the abnormal motor performance observed in ataxic rats. To investigate whether such changes in the intrinsic neuronal excitability could be attributed to the role of Ca(2+)-activated K(+) channels (K(Ca)), whole cell current clamp recordings were made from PCs in cerebellar slices of control and ataxic rats. 3-AP induced profound alterations in the intrinsic properties of PCs, as evidenced by a significant increase in both the membrane input resistance and the initial discharge frequency, along with the disruption of the firing regularity. In control PCs, the blockade of small conductance K(Ca) channels by UCL1684 resulted in a significant increase in the membrane input resistance, action potential (AP) half-width, time to peak of the AP and initial discharge frequency. SK channel blockade also significantly decreased the neuronal discharge regularity, the peak amplitude of the AP, the amplitude of the afterhyperpolarization and the spike frequency adaptation ratio. In contrast, in ataxic rats, both the firing regularity and the initial firing frequency were significantly increased by the blockade of SK channels. In conclusion, ataxia may arise from alterations in the functional contribution of SK channels, to the intrinsic properties of PCs.
Neuroscience Research Centre and Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
M
M
Kaffashian
M
M
Shabani
I
I
Goudarzi
G
G
Behzadi
A
A
Zali
M
M
Janahmadi
D000200:Action Potentials / Q000187:drug effects; D000473:Alkanes / Q000494:pharmacology; D000818:Animals; D002524:Cerebellar Ataxia / Q000139:chemically induced / Q000503:physiopathology*; D009498:Neurotoxins / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D011806:Quinolinium Compounds / Q000494:pharmacology; D051381:Rats; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*
C110349:6,10-diaza-3(1,3),8(1,4)dibenzena-1,5(1,4)diquinolinacyclodecaphane; D000473:Alkanes; D009498:Neurotoxins; D011725:Pyridines; D011806:Quinolinium Compounds; D051640:Small-Conductance Calcium-Activated Potassium Channels; C010835:3-acetylpyridine