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Iberiotoxin-sensitive and -insensitive BK currents in Purkinje neuron somata
Mark D Benton1, Amanda H Lewis, Jason S Bant
1Interdepartmental Neuroscience Program, Northwestern University, Evanston, Illinois, USA.
Journal of Neurophysiology
|March 1, 2013
Summary
Purkinje cells have two distinct calcium-activated potassium (KCa) currents. These currents, one sensitive and one insensitive to iberiotoxin, influence neuronal firing and may be targets for treating ataxia.
Area of Science:
- Neuroscience
- Cellular Electrophysiology
- Ion Channel Physiology
Background:
- Purkinje cells are crucial for motor control and possess unique ionic conductances for high-frequency firing.
- Disruptions in calcium (Ca) or Ca-activated potassium (KCa) currents in Purkinje cells are linked to motor deficits and altered neuronal activity.
- Understanding the properties of somatic KCa currents is essential for elucidating Purkinje cell function and dysfunction.
Purpose of the Study:
- To characterize the properties of somatic KCa currents in Purkinje cells.
- To investigate the pharmacological and biophysical characteristics of IBTX-sensitive and IBTX-insensitive KCa currents.
- To explore the role of these currents in Purkinje cell firing patterns and their potential modulation.
Main Methods:
- Voltage-clamp recordings of KCa currents in isolated mouse Purkinje cell bodies.
- Evocation of currents using endogenous Ca influx under physiological Ca buffering conditions.
- Application of various KCa channel blockers (IBTX, apamin, TEA) and agonists (EBIO, chlorzoxazone, CyPPA).
Main Results:
- Purkinje somata exhibit voltage-activated, Cd-sensitive KCa currents with distinct IBTX-sensitive and IBTX-insensitive components.
- IBTX-sensitive currents showed rapid activation and inactivation, while IBTX-insensitive currents activated slowly and did not inactivate.
- IBTX-insensitive currents, likely mediated by BK channels, were modulated by KCa channel agonists, affecting firing patterns.
- Agonist-induced augmentation of BK current may contribute to alleviating disrupted Purkinje cell firing in ataxias.
Conclusions:
- Purkinje cell somata possess at least two functionally distinct KCa current components carried by large-conductance (BK) channels.
- These KCa current components differentially contribute to Purkinje cell repolarization and firing rate regulation.
- Modulation of BK currents by specific agonists shows therapeutic potential for genetic ataxias affecting Purkinje cell function.
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