Developmental Maturation of Voltage-Gated Potassium Channels in the Medial Nucleus of the Trapezoid Body

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Nikollas Moreira Benites

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Abstract

Principal neurons in the medial nucleus of the trapezoid body (MNTB) express diverse voltage-gated potassium (Kv) channels, which play a crucial role in shaping action potentials. In adult mice, Kv1, Kv3, and Kv4 subfamilies have been identified in the MNTB, but their developmental processes remain poorly understood. Previous studies suggest that Kv1 channels emerge concurrently with establishing the Calyx of Held. Kv1 and Kv4 are low-voltage activated potassium (LVA) channels, requiring prior hyperpolarization for full activation. LVA channels influence the action potential threshold, opening near the resting potential. Kv3 channels are high-voltage activated potassium (HVA) channels primarily affecting action potential repolarization. We employed two voltage-clamp protocols using P1-P6 FVB mice to investigate these conductances. Protocol 1 involved depolarizing steps of 300 ms, from -113mV to 32mV, in 5mV increments, with a holding potential of -73mV. Protocol 2 comprised a double-test pulse preceded by a 200ms step to -123mV to remove steady-state inactivation of Kv4 channels. The second pulse included a pre-pulse of 50ms of -43mV to inactivate Kv4 channels. The test pulse in Protocol 2 consisted of 10mV steps from -73mV to 27mV for 200ms. The synaptic inhibitors strychnine, gabazine, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), as well as tetrodotoxin and isradipine or Cd+2. We administered dendrotoxin to evaluate Kv1 and TEA to access Kv3. Kv4 was assessed by subtracting the second pulse from the first pulse test in Protocol 2.

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Brazil

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College of Engineering

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Biomedical Engineering

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George Spirou

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Event

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Developmental Maturation of Voltage-Gated Potassium Channels in the Medial Nucleus of the Trapezoid Body

Principal neurons in the medial nucleus of the trapezoid body (MNTB) express diverse voltage-gated potassium (Kv) channels, which play a crucial role in shaping action potentials. In adult mice, Kv1, Kv3, and Kv4 subfamilies have been identified in the MNTB, but their developmental processes remain poorly understood. Previous studies suggest that Kv1 channels emerge concurrently with establishing the Calyx of Held. Kv1 and Kv4 are low-voltage activated potassium (LVA) channels, requiring prior hyperpolarization for full activation. LVA channels influence the action potential threshold, opening near the resting potential. Kv3 channels are high-voltage activated potassium (HVA) channels primarily affecting action potential repolarization. We employed two voltage-clamp protocols using P1-P6 FVB mice to investigate these conductances. Protocol 1 involved depolarizing steps of 300 ms, from -113mV to 32mV, in 5mV increments, with a holding potential of -73mV. Protocol 2 comprised a double-test pulse preceded by a 200ms step to -123mV to remove steady-state inactivation of Kv4 channels. The second pulse included a pre-pulse of 50ms of -43mV to inactivate Kv4 channels. The test pulse in Protocol 2 consisted of 10mV steps from -73mV to 27mV for 200ms. The synaptic inhibitors strychnine, gabazine, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), as well as tetrodotoxin and isradipine or Cd+2. We administered dendrotoxin to evaluate Kv1 and TEA to access Kv3. Kv4 was assessed by subtracting the second pulse from the first pulse test in Protocol 2.