Research ReportPotassium-selective microelectrode revealed difference in threshold potassium concentration for cortical spreading depression in female and male rat brain
Graphical Abstract
Research Highlights
► Potassium-selective microelectrodes (ISE) were inserted into rat cortex. ► Spreading depression (SD) was started by application of 1 M KCl. ► Threshold for SD was 14 mM K+ in males, but only 8 mM for females. ► Lower K+ threshold can explain the predisposition of women to migraine.
Introduction
During nerve impulses, sodium enters the nerve cells and potassium leaks out (Hodgkin and Huxley, 1952). With the great density of neurons and glial cells in the brain, intensive neural activity may induce an accumulation of extracellular K+ ([K+]e) causing depolarization of adjacent neurons and glial cells and the generation or blockade of impulses. Leäo's spreading depression (SD) of cortical activity is a fine example of such a process. SD is characterized by a prominent negative slow field potential wave (FP) that lasts approximately 20–60 s and reaches 10–30 mV in amplitude. This wave is accompanied by a dramatic release of potassium from the cells. The absolute potassium activity in the extracellular space during SD was directly recorded by a potassium-selective microelectrode for the first time in 1972 (Vyskočil et al., 1972). This abrupt K+ release increases the [K+]e from resting 3 to 60 mM 1–2 mm below the cortical surface and leads to an almost complete depolarization of cortical cells. Most probably the increase in [K+]e, together with glutamate release (Jing et al., 1993, Marrannes et al., 1988) and other factors (Bogdanov et al., in press, Rogawski, 2008, Smith et al., 2006, Somjen et al., 1992, Somjen, 2001), contributes to a progressive propagation of SD.
In recent years, SD has been linked with the onset of migraine, in particular with aura (Bogdanov et al., in press, Hadjikhani et al., 2001) which predominantly affects women (Lipton et al., 2001). The specific mechanisms that are responsible for the increased prevalence of migraine in women have not been definitively identified. It has been found that female mice have a significantly reduced electric threshold for SD compared with male mice, suggesting an intrinsic difference in cortical excitability that may be involved in the predisposition to migraine (Brennan et al., 2007). The aim of this report was to verify directly whether this gender difference might be determined not only by electric threshold but also by a difference in the critical K+ concentration eliciting the SD from sites that are already depolarized. Using a potassium-selective microelectrode technique, we found that the threshold [K+]e concentration for the initiation of SD in the extracellular space of the cerebral cortex in the female rat brain is slightly more than half than in the male rat.
Section snippets
Results
Potassium transients and the onset of SD were recorded either approximately 5 or 1.5 mm from the site of 1 M KCl application (Fig. 1 inset). Recordings were made with a double-barrelled potassium-sensitive microelectrode inserted 1 mm under the cortex surface. When the distance between the rostral and proximal trephines for the administration of 1 M KCl and for potassium recording respectively was several millimeters, the [K+]e wave followed a smooth course from which the threshold for SD
Discussion
It was found that the critical [K+]e for eliciting the fast SD wave of extracellular potassium is 80% higher in the male rat cortex than in the female one. This finding correlates well with recently published data on the reduced electric and chemical threshold in female rats (Brennan et al., 2007) and points to Nernstian depolarization as one of the most important triggers of SD. The rate of the first slow phase of [K+]e increase in the measurement site was close to the rate of [K+]e increase
Electrophysiology
Changes in [K+]e and field potential in the cortex were measured at a depth of 1 mm with double-barrelled, K+-selective/reference microelectrodes. The microelectrodes were pulled to tips approximately 2 μm in diameter from double-barrelled glass prefabricates (Kavalier a. s., Czech Republic, each barrel was 2 mm in diameter) according to the procedure described in detail elsewhere (Vyskočil and Kříž, 1972). After being coated with silicone, the tip of one microelectrode channel was filled by
Acknowledgments
This study was supported by grants IAA500110905 and AV0Z 0110509.
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