Baicalin enhances middle cerebral artery smooth muscle cells BK channel-mediated outward currents in SD rats / 中国药理学通报

Aim To study the effeet of baicalin on middle cerebral arterv in SD rats.Methods The j changes of middle cerebral artery diameter were observed using a pressure myograph system.The whole- cell and inside-out patch-clamp recording were used to detected the electrophysiological features of single vascular smooth muscle cells.Results Baicalin dilated the middle cerebral artery segment of SD rats in a con- centration-dependent manner.IbTX blocked baicalin - mediated relaxation.Baicalin enhanced the outward current of middle cerebral artery smooth muscle cells in a concentration-dependent manner.IbTX blocked ba- icalin-mediated outward current.Baicalin increased BK channel open probabilities.Conclusions Baicalin enhances the outward current mediated by BK channel and relaxes the middle cerebral arterv in SD rats.

Bisphenol A and 4-tert-Octylphenol Inhibit Cx46 Hemichannel Currents

Connexins (Cx) are membrane proteins and monomers for forming gap junction (GJ) channels. Cx46 and Cx50 are also known to function as conductive hemichannels. As part of an ongoing effort to find GJ-specific blocker(s), endocrine disruptors were used to examine their effect on Cx46 hemichannels expressed in Xenopus oocytes. Voltage-dependent gating of Cx46 hemichannels was characterized by slowly activating outward currents and relatively fast inward tail currents. Bisphenol A (BPA, 10 nM) reduced outward currents of Cx46 hemichannels up to ~18% of control, and its effect was reversible (n=5). 4-tert-Octylphenol (OP, 1 microM) reversibly reduced outward hemichannel currents up to ~28% (n=4). However, overall shapes of Cx46 hemichannel current traces (outward and inward currents) were not changed by these drugs. These results suggest that BPA and OP are likely to occupy the pore of Cx46 hemichannels and thus obstruct the ionic fluxes. This finding provides that BPA and OP are potential candidates for GJ channel blockers.

Biphase actions of galanin antagonists at different doses on galanin-evoked outward-current of trigeminal nucleus neurons in rats / 中国临床药理学与治疗学

Aim To observe the effects of galanin (Gal) antagonist M35 or M40 at different concentrations on the Gal evoked outward current in principal trigeminal nucleus (PrV) neurons. Methods The technique of whole cell patch clamp was used to record the change of membrane current. Results At doses of M35 0.01 , 0.03 and 0.1 ?mol?L -1 , the Gal evoked outward current decreased by 53.1 %, 40.4 % and 27.2 %,respectively. While M35 1 and 3 ?mol?L -1 , the current increased by 16.2 % and 38.4 %. At doses of M40 0.01 and 0.03 ?mol?L -1 ,the current increased by 93.7 % and 68.4 %,while for M40 0.3 ,1 and 3??mol?L -1 , the current decreased by 49.2 %, 69.9 % and 87.2 %, respectively. Conclusion M35 at low concentrations antagonizes the effect of Gal and at high concentrations acts as a Gal receptor agonist. Whereas M40 in high doses antagonizes the effect of Gal and in low doses exerts an autagonistic action. There may be different Gal subtype receptors in the same PrV neuron.

Blockade of intrinsic oscillatory activity of cerebellar Purkinje cells by apamin and nickel

Intracellular recordings of oscillatory firing (bursting activity) were obtained from Purkinje cells (PCs) in rat cerebellar slices. Apamin inhibited post-burst hyperpolarizations (PBHs) progressively and finally terminated oscillatory firing activity of PCs. Apamin did not affect the amplitude or duration of the after-hyperpolarization (AHP) between spikes within the burst. In the voltage clamp mode, apamin shifted the whole-cell, quasi-steady state I/V relationship in an inward direction and abolished the zero slope resistance (ZSR) region by blocking outward current. Nickel (Ni2+) terminated oscillatory activity and also abolished the ZSR region. However, Ni2+ did not have progressive blocking action on the post-burst hyperpolarization before it blocked oscillatory activity. Ni2+ blocked an inward current at potentials positive to approximately -65 mV, which was responsible for the ZSR region and outward current at more negative potentials. These data indicated that oscillatory activity of PCs is sustained by a balance between a slow Ni2+ -sensitive inward current and an apamin-sensitive outward current in the region of ZSR of the whole-cell I/V curve.