• 한국자기공명학회논문지
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• 제22권1호
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• pp.1-9
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• 2018

Among several NMR hyperpolarization techniques, parahydrogen-based hyperpolarization technique is recently extensively utilized to enhance the sensitivity of the conventional NMR/MRI spectroscopy. Two mostly investigated research topics are PHIP (Parahydrogen Induced Polarization) and SABRE (Signal Amplification By Reversible Exchange), which are commonly using the parahydrogen as the source of hyperpolarization. Those researches have been considered as the promising techniques that could provide hyperpolarized states on the ambient substrates including biologically important materials. Therefore, based on their potentials, we briefly reviewed several important experimental results on those topics after introducing the basic principle of parahydrogen and its generation with conceptual explanations. We hope this review will broaden the parahydrogen-based hyperpolarization transfer study on many researches in Korea.

• 한국자기공명학회논문지
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• 제24권1호
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• pp.9-15
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• 2020

Nitrogen vacancy center (NV center) in diamond has recently been appeared as a promising candidate for hyperpolarization applications due to its optical pumping property by laser. Optically Detected Magnetic Resonance (ODMR) has been used as a conventional method to obtain the resonance spectrum of NV centers. ODMR, however, has a shortcoming of sensitivity and a limitation of subjects, such that the degree of hyperpolarization can hardly be estimated, and that the spins other than NV centers are invisible. In contrast, Electron Spin Resonance (ESR) spectroscopy is known to proportionally reflect the degree of spin polarization. In this work, we successfully observed the optically-induced hyperpolarization of NV spins in diamond through CW-ESR spectroscopy with an X-band system. All the NV peaks were identified by calculating the eigenvalues of NV spin Hamiltonian. The intensities of NV peaks were enhanced over 240 times after optical pumping. The enhanced peaks corresponding to the transition from |m_s=0> to |m_s=-1> revealed inverted phases, while other peaks remained in-phase. The optically-induced hyperpolarization on NV spins can be a useful polarization source, leading to ¹³C nuclear hyperpolarization in diamond.

• 한국자기공명학회논문지
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• 제23권1호
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• pp.6-11
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• 2019

Parahydrogen induced hyperpolarization (PHIP) technique is extensively studied to increase the sensitivity of the conventional NMR spectroscopy and recently try to apply this advanced technique into the revolutionary future of the MRI. The other hyperpolarization technique, which is widely utilized, is DNP (Dynamic Nuclear Polarization)-based hyperpolarization one. Despite its great advances in these fields, it contains several drawbacks to overcome: fast relaxation time, expensive equipment is needed, long build-up time is required (several hours), and batch scale material is hyperpolarized. To overcome all those limitations, one can effectively harness the hyperpolarized spin state of parahydrogen. One important step for utilizing the spin state of parahydrogen is doing well-developed experiments of ALTADENA and PASADENA. Based on those concepts, we successfully obtain the hydrogenation signals of ALTADENA and PASADENA from styrene by using benchtop NMR spectrometer. Also those signals were conceptually analyzed and confirmed with different mechanisms. To our best knowledge, those experiments using 1.4T (benchtop NMR) is the first reported one. Considering these experiments, we hope that parahydrogen-based hyperpolarization transfer studies in NMR/MRI will be broadened in Korea in the future.

• 한국자기공명학회논문지
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• 제25권4호
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• pp.64-69
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• 2021

In the developed NMR hyperpolarization techniques, Signal amplification by reversible exchange (SABRE) technique is thought to be a promising method to overcome the low sensitivity of bio-NMR/MRI. Most experiments using SABRE have been done in methanol, which is biologically harmful solvent. Therefore, more biological friendly solvent, such as ethanol can be more appropriate solvent to be applicable in bio-NMR and MRI. As the proof of concept, successful hyperpolarization on pyridine via SABRE is carried out in ethanol and its enhancement factor is calculated to be more than 150 folds. To investigate more about its possibility of hyperpolarization in different alcohol solvents, methanol and propanol are used for SABRE in the same condition. The overall polarization trend in different external magnetic field is similar but its polarization number is decreased with higher molecular weight solvents (the order from methanol to propanol). This result indicates that the efficiency of SABRE is different from solvent system despite its same functional group and similar properties. Higher para-hydrogen concentration, higher partial pressure of para-hydrogen, and deuterated solvent can increase the hyperpolarization in any solvents. With these series of successful SABRE results, future studies on SABRE in more biofriendly environment, on more various solvent systems, and with more substrates are needed and it will be the firm basis for applying the SABRE system on the future bio-NMR/MRI.

• 한국자기공명학회논문지
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• 제19권3호
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• pp.124-131
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• 2015

Hyperpolarization methods are the most emerging techniques in the field of magnetic resonance (MR) researches since they make a contribution to overcoming sensitivity limitation of MR spectroscopy and imaging, leading to new fields of researches, real-time in vivo metabolic/molecular imaging and MR analysis of chemical/biological reactions in non-equilibrium conditions. Make use of enormous signal enrichments, it becomes feasible to investigate various chemical and biochemical systems with low ${\gamma}$ nuclei in real-time. This review deals with the theoretical principals of common hyperpolarization methods and their experimental features. In addition, more detailed theories, mechanisms, and applications of dissolution dynamic nuclear polarization (D-DNP) are discussed.

• The Korean Journal of Physiology
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• 제19권2호
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• pp.113-125
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• 1985

Electrophysiological difference of the central and peripheral area of the sinoatrial node in the rabbit was studied by glass microelectrode technique. Effects of $K^+,\;Na^+,\;Cs^+,$ adrenaline and ouabain on the action potential of the two areas were investigated, and transient hyperpolarization ($K^+-induced$ hyperpolarization) which developed following readmission of potassium after having pre-treated with $K^+-free$ Tyrode solution for 10 minutes was analyzed. The results obtained were as follows ; 1) The frequency of the spontaneous action potential recorded in the periphery of the SA node was faster than the central area. Reduction by $Cs^+$ and increase by O mM $K^+$, $10^{-6}M$ adrenaline and $10^{-6}M$ ouabain in the frequency of action potential were noticed more prominently in the peripheral than the central area. On the contrary, the frequency in the central area was more decreased than the Peripheral area by 13 mH $K^+$ and 1 mM $Co^{2+}$. 2) The amplitude of the K+_induced hyperpolarization was very small in the central area but large in the peripheral area. Transient hyperpolarization was abolished by ouabain and low sodium, and decreased by cooling the tissue $(17^{\circ}C)$. 3) By changing the concentration of $Ca^{2+}$ in the perfusate, the amplitude and the rate of transient hyperpolarization were increased in the high $Ca^{2+}$ concentration. It could be concluded that the central area of the SA node is less susceptible to the inhibition of Na-Pump and more susceptible to Ca-blocker and high concentration of $K^+$. The Na-Pump activity of the central area measured by means of transient hyperpolarization is found to be much less active than that of the peripheral area.

• 약학회지
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• 제56권2호
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• pp.108-115
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• 2012

The hyperpolarization-activated current ($I_h$) is an inward cation current activated by hyperpolarization of the membrane potential and plays a role as an important modulator of action potential firing frequency in many excitable cells. In the present study we investigated the effects of extracellular divalent cations on $I_h$ in dorsal root ganglion (DRG) neurons using whole-cell voltage clamp technique. $I_h$ was slightly increased in $Ca^{2+}$-free bath solution. BAPTA-AM did not change the amplitudes of $I_h$. Amplitudes of $I_h$ were decreased by $Ca^{2+}$, $Mg^{2+}$ and $Ba^{2+}$ dose-dependently and voltage-independently. Inhibition magnitudes of $I_h$ by external divalent cations were partly reversed by the concomitant increase of extracellular $K^+$ concentration. Reversal potential of $I_h$ was significantly shifted by $Ba^{2+}$ and $V_{1/2}$ was significantly affected by the changes of extracellular $Ca^{2+}$ concentrations. These results suggest that $I_h$ is inhibited by extracellular divalent cations ($Ca^{2+}$, $Mg^{2+}$ and $Ba^{2+}$) by interfering ion influxes in cultured rat DRG neurons.

• International Journal of Oral Biology
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• 제40권4호
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• pp.211-216
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• 2015

Nitric Oxide (NO) is an important signaling molecule in the nociceptive process. Our previous study suggested that high concentrations of sodium nitroprusside (SNP), a NO donor, induce a membrane hyperpolarization and outward current through large conductances calcium-activated potassium ($BK_{ca}$) channels in substantia gelatinosa (SG) neurons. In this study, patch clamp recording in spinal slices was used to investigate the sources of $Ca^{2+}$ that induces $Ca^{2+}$-activated potassium currents. Application of SNP induced a membrane hyperpolarization, which was significantly inhibited by hemoglobin and 2-(4-carboxyphenyl) -4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt (c-PTIO), NO scavengers. SNP-induced hyperpolarization was decreased in the presence of charybdotoxin, a selective $BK_{Ca}$ channel blocker. In addition, SNP-induced response was significantly blocked by pretreatment of thapsigargin which can remove $Ca^{2+}$ in endoplasmic reticulum, and decreased by pretreatment of dentrolene, a ryanodine receptors (RyR) blocker. These data suggested that NO induces a membrane hyperpolarization through $BK_{ca}$ channels, which are activated by intracellular $Ca^{2+}$ increase via activation of RyR of $Ca^{2+}$ stores.

• BMB Reports
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• 제28권3호
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• pp.221-226
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• 1995

Dopamine mediates inhibitory responses in Helix aspersa neurons from the right parietal lobe ("F-lobe") of the circumoesophageal ganglia. The effects appeared as a dose-dependent hyperpolarization of the plasma membrane and a decrease in the occurrence of spontaneous action potentials. The average hyperpolarization with 5 ${\mu}m$ dopamine was -12 mV (${\pm}1.5$mV, S.D., n=12). Dopamine also modulated the currents 'responsible for shaping the action potentials in these neurons. When dopamine was added and action potentials were triggered by an injection of current, the initial depolarization was slowed, the amplitude and the duration of action potentials were decreased, and the after-hyperpolarization was more pronounced. The amplitude and the duration of action potential were reduced about 15 mV and about 13% by 5 ${\mu}m$ dopamine, respectively. The effects of dopamine on the resting membrane potentials and the action potentials of Helix neurons were dose-dependent in the concentration range 0.1 ${\mu}m$ to 50 ${\mu}m$. In order to show 1) that the effects of dopamine were mediated by dopamine receptors rather than by direct action on ionic channels and 2) which type of dopamine receptor might be responsible for the various effects, we assayed the ability of mammalian dopamine receptor antagonists, SCH-23390 (antagonist of D1 receptor) and spiperone (antagonist of D2 receptor), to block the dopamine-dependent changes. The D1 and D2 antagonists partially inhibited the dopamine-dependent hyperpolarization and the decrease in action potential amplitude. They both completely blocked the decrease in action potential duration and the increase in action potential after-hyperpolarization. The dopamine-induced slowdown of the depolarization in the initial phase of the action potentials was less effected by SCH-23390 and spiperone. From the results we suggest 1) that Helix F-lobe neurons may have a single type of dopamine receptor that binds both SCH-23390 and spiperone and 2) that the dopamine receptor of Helix F-lobe neurons may be homologous with and primitive to the family of mammalian dopamine receptors.

• The Korean Journal of Physiology and Pharmacology
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• 제5권1호
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• pp.1-8
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• 2001

Hyperpolarization of arterial smooth muscle by acetylcholine is considered to be produced by the release of an unidentified chemical substance, an endothelium-derived hyperpolarizing factor (EDHF). Several chemicals have been proposed as the candidate for EDHF. However, none of them fulfil completely the nature and property of EDHF. Ultrastructural observation with electron microscope reveals that in some arteries, gap junctions are formed between endothelial and smooth muscle cells. In small arterioles, injection of gap junction permeable dyes into an endothelial cell results in a distribution of the dye to surrounding cells including smooth muscle cells. These observations allow the speculation that myoendothelial gap junctions may have a functional significance. Simultaneous measurement of the electrical responses in both endothelial and smooth muscle cells using the double patch clamp method demonstrates that these two cell types are indeed electrically coupled, indicating that they behave as a functional syncytium. The EDHF-induced hyperpolarization is produced by an activation of $Ca^{2+}-sensitive\;K^+-channels$ that are inhibited by charybdotoxin and apamin. Agonists that release EDHF increase $[Ca^{2+}]_i$ in endothelial cells but not in smooth muscle cells. Inhibition of gap junctions with chemical agents abolishes the agonist-induced hyperpolarization in smooth muscle cells but not in endothelial cells. All these observations can be explained if EDHF is an electrotonic signal propagating from endothelium to smooth muscle cells through gap junctions.