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Potassium and sodium channels in human malignant glioma cells
1Department of Clinical Neurophysiology, Karolinska Hospital, Stockholm, Sweden.
Abstract:
Human malignant glioma cells from 5 different cell lines were voltage clamped and examined for the presence of depolarization-activated ion channels. Outward K-currents were elicited at membrane potentials greater than 40 mV, which had two main components, one which was delayed and blocked by externally applied tetraethylammonium (TEA, 10 mM), and another which was instantaneous and insensitive to TEA in the outside solution. The proportion of the two K-current components varied between cell lines. An increase in [Ca2+]o in the range 0-4 mM, decreased the leak conductance and shifted the activation of the instantaneous outward K-current towards more positive potentials. Mg2+, Zn2+ and Co2+ had qualitatively similar effects. Patch recordings with 150-160 mM K+-solution on both sides of the membrane revealed that the delayed outward K-current was carried through large conductance (250-300 pS) channels. Changes in free [Ca2+]i from 0 to 2 x 10(-8) M increased the activation of the large conductance K-channel. Small Na-currents were identified in cells from one cell line (Tp-378MG). The Na-conductance ranged from 0.5 to 7.5 nS in 25% of the cells, and was less than 0.5 nS in 75%. The Na-channels were activated and inactivated at 30-40 mV more positive potentials than in the mammalian peripheral nerve. Tetrodotoxin (100 nM) blocked gNa almost completely.
Insights
Human malignant glioma cells exhibit distinct outward potassium currents, with varying components sensitive to calcium and other divalent cations. Sodium currents were also identified, differing from those in peripheral nerves.
Area of Science:
- Neuroscience
- Cell Biology
- Ion Channel Physiology
Background:
- Malignant gliomas are aggressive brain tumors.
- Understanding ion channel function is crucial for glioma research.
Purpose of the Study:
- To investigate depolarization-activated ion channels in human malignant glioma cells.
- To characterize the properties of potassium and sodium currents in these cells.
Main Methods:
- Voltage clamp electrophysiology on 5 human malignant glioma cell lines.
- Patch clamp recordings to identify channel conductance.
- Application of tetraethylammonium (TEA), calcium, magnesium, zinc, cobalt, and tetrodotoxin (TTX).
Main Results:
- Two outward potassium current components were identified: a delayed TEA-sensitive current and an instantaneous TEA-insensitive current.
- Extracellular calcium, magnesium, zinc, and cobalt modulated leak conductance and potassium current activation.
- Large conductance (250-300 pS) potassium channels were involved in the delayed outward current, modulated by intracellular calcium.
- Small sodium currents were observed in one cell line, with distinct activation/inactivation potentials and sensitivity to TTX.
Conclusions:
- Human malignant glioma cells possess complex outward potassium currents with varying characteristics.
- Divalent cations play a significant role in modulating glioma cell ion channel activity.
- Glioma sodium channels exhibit unique electrophysiological properties compared to mammalian peripheral nerve sodium channels.