• 제목/요약/키워드: Ion channels

검색결과 259건 처리시간 0.022초

광유전학: 세포 생리 연구를 위한 새로운 frontier (Optogenetics: a New Frontier for Cell Physiology Study)

  • 변종회
    • 생명과학회지
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    • 제25권8호
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    • pp.953-959
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    • 2015
  • 광유전학은 생체 조직 및 세포에서 유전공학적으로 발현된 광민감성 단백질을 이용하여 목표로 하는 분자/세포 활동을 조절하기 위한 광학 및 분자적 전략들의 조합이다. 광유전학은 빛을 이용하여 신경세포의 발화 여부를 결정하는 세포막 채널을 빨리 열고 닫는 방법을 포함한다. 이 기술은 녹조류의 광민감성 단백질들을 특정 뇌세포에 넣는데서 시작되었다. 이렇게 하면 세포들은 파랑이나 노락색의 펄스로 켜지거나 꺼질 수 있다. 빨리 개폐되는 광민감성 양이온 채널인 자연계에 존재하는 조류 단백질인 channelrhodopsin-2 (ChR2)를 이용하여 활동전위의 숫자와 빈번도를 조절할 수 있다. ChR2는 다른 세포들은 영향을 주지 않으면서 한 유형의 신경세포만 조작할 수 있는 길을 제시하는데, 이는 전례가 없는 특이성이다. 이 기술은 빛을 이용하여 단일 발화와 시냅스 사건 수준에서 신경신호전달을 변경시킬 수 있도록 하여 신경과학자와 의생명공학자들에게 널리 적용될 수 있는 도구를 제공한다. 녹조류와 레이저, 유전자 치료, 광섬유의 희한한 조합은 이전에 결코 불가능했던 정밀도로 뇌 속 깊은 곳의 신경 회로 지도를 그릴 수 있도록 해주었다. 이것은 우울증, 불안, 정신분열, 중독, 수면병, 그리고 자폐증 같은 질환의 원인을 밝히는데 도움을 줄 것이다. 광유전학은 파킨슨병, 강박장애, 그리고 전기 펄스가 있는 다른 질환들을 치료하는데 사용되는 기존 이식 도구들을 개선시킬 수 있다. 광유전학 장치는 상기 장치들이 할 수 있는 것보다 더 많이 뇌세포의 특정 세포들을 대상으로 할 수 있다. 신경세포 이외의 일반 세포들에도 광유전학 도구들을 적용하는 연구들이 증가하고 있다.

Mouse 갑상선에서 α1-adrenoceptor 자극에 의한 thyroxine 유리 억제기전 (Inhibitory mechanism of α1-adrenergic stimulation on the release of thyroxine in mouse thyroids)

  • 강형섭;김송규;강창원;김진상;이호일
    • 대한수의학회지
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    • 제38권4호
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    • pp.712-719
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    • 1998
  • Thyroid function is mainly regulated through cAMP and phophatidylinositol, and it is well known that TSH-stimulated thyroxine ($T_4$) release is inhibited by catecholamine from mouse thyroids via the ${\alpha}_1$-adrenoceptor stimulation. Previous study has established that the inhibition of $T_4$ release by ${\alpha}_1$-adrenoceptor stimulation results in activated protein kinase C (PKC). The purpose of this study was to determine if ion transport systems are involved in the inhibition of $T_4$ release elicited by ${\alpha}_1$-adrenergic agonist in mouse thyroids. TSH-, IBMX- and cAMP analogue-stimulated $T_4$ release were significantly inhibited by methoxamine, R59022 (diacylglycerol kinase inhibitor), and MDL (adenylate cyclase inhibitor). TSH-stimulated $T_4$ release could be inhibited by Bay K 8644 and cyclopiazoic acid, but not by verapamil and tetrodotoxin. The addition of nifedipine ($Ca^{2+}$ channel blocker), tetrodotoxin and lidocaine ($Na^+$ channel blockers), but not amiloride (EIPA) and ryanodine, completely blocked the inhibitory effects of methoxamine on $T_4$ release. TSH-stimulated $T_4$ release was also inhibited by benzamil ($Na^+-Ca^{2+}$ exchange inhibitor). TSH-, IBMX- and cAMP-stimulated $T_4$ release were inhibited by methoxamine or R59022, these effects were reversed by nifedipine. but not by verapamil. Furthermore, nifedipine reversed the inhibitory effects of benzamil and R59022 on TSH-stimulated $T_4$ release. These data suggest that the observed ${\alpha}_1$-adrenoceptor-mediated inhibition of $T_4$ release in mouse thyroids is the result of an increase in intracellular $Na^+$ or $Ca^{2+}$ effected via activation of fast $Na^+$ or nifedipine-sensitive $Ca^{2+}$ channels, and that $Na^+-Ca^{2+}$ exchange may play an important role in reducing thyroid hormone by increasing intracellular $Ca^{2+}$.

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신생흰쥐 척수후근신경절 세포에서 전압의존성 $K^+$ 전류의 동정 (Characterization of Voltage-Gated Potassium Currents in Dorsal Root Ganglion Neurons of Neonatal Rats)

  • 김지목;정승준;김상정;김전
    • The Korean Journal of Physiology and Pharmacology
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    • 제1권6호
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    • pp.613-624
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    • 1997
  • Dorsal root ganglion (DRG) is composed of neuronal cell bodies of primary afferents with diverse functions. Various types of ion channels present on DRG neurons may reflect those functions. In the present study, voltage-gated potassium currents in DRG neurons of neonatal rats were characterized by whole-cell voltage clamp method. Two types of delayed rectifier and three types of transient potassium currents were identified according to their electrophysiological properties. The delayed rectifier currents were named $I_{Ke}$ (early inactivating) and $I_{K1}$ (late inactivating). Steady state inactivation of $I_{Ke}$ began from -100 mV lasting until -20 mV. $I_{K1}$ could be distinguished from $I_{Ke}$ by its inactivation voltage range, from -70 mV to +10 mV. Three transient currents were named $I_{Af}$ (fast inactivation), $I_{Ai}$ (intermediate inactivation kinetics), and $I_{As}$ (slow inactivation). $I_{Af}$ showed fast inactivation with time constant of $10.6{\pm}2.0$ msec, $I_{Ai}$ of $36.9{\pm}13.9$ msec, and $I_{As}$ of $60.6{\pm}2.9$ msec at +30 mV, respectively. They also had distinct steady state inactivation range of each. Each cell expressed diverse combination of potassium currents. The cells most frequently observed were those which expressed both $I_{K1}$ and $I_{Af}$, and they had large diameters. The cells expressing $I_{Ke}$ and expressing $I_{Ke}$, $I_{Ai}$, and $I_{As}$ usually had small diameters. Judging from cell diameter, capsaicin sensitivity or action potential duration, candidates for nociceptor were the cells expressing $I_{Ke}$, expressing $I_{Ke}$ and $I_{Ai}$, and expressing $I_{Ke}$ and $I_{As}$. The types and distribution of potassium currents in neonatal rat DRG were similar to those of adult rat DRG (Gold et al, 1996b).

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경상남도 남강유역의 의용패류 분포 및 흡충류 유충 감염실태 조사 (Distribution of medically important freshwater snails and larval trematodes from Parafossarulus manchouricus and Semisulcospira libertina around the Jinyang Lake in Kyongsang-Nam-Do, Korea)

  • 조해창;정평림이근태
    • Parasites, Hosts and Diseases
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    • 제21권2호
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    • pp.193-204
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    • 1983
  • The Jinyang Lake is dammed up Nam River, and surrounded by Jinju city and four counties; Jinyang, Sanchong, Hading, and Sachon in kyongsang-Nam-Bo, Korea. The areas around this man-made lake have been known as an endemic focus of clonorchiasis in Korea. The present study was first aimed to know the distribution of freshwater mollusks including medically important snails, and larval trematodes shed from Parafossarulus manchouricus and Semisulcospira libertina. In addition to above studies, water analyses in each snail habitat were carried out in order to figure out a part of their environmental factors. This malaco-ecological survey was done at the sirs areas around upper, middle and lower parts of the lake for 4 months, August-November, 1983. Total nine species of freshwater mollusks were collected throughout the study: 4 species of gastropods: Semisulcospira libertina, Cipangopaludina chinensis, Parafossarulus manchouricus and Radin auricularia, and 5 species of bit.alves; Unio dcuglasiae, Ancdonta woodiana, Lamprotula gottschei, Corbicula yuminea and Limncperma lucustris. Out of nine species of freshwater mollusks, three species of gastropods; S. Zibertina, p. manchouricus and R. auricularia were medically important in terms of the transmission of digenetic trematodes to humans. P. manchouricus and R. auricularia were mainly collected from the shallow ponds and the irrigation channels with the muddy basin, but S. libertine and the bivalves were only collected from the stream of Nam River where the gravels and rocks were dominant. The levels of dissolved oxygen (D.O.) and biochemical oxygen demand \(B.O.D._5)\ of the water specimens sampled from the study areas ranged from 6.0 to 9.6 ppm and from 0.4 to 1.6 ppm respectively. As a result, it is considered that water system around the Jinyang Lake might be relatively clean without any heavy pollution of aquatic microorganisms and organic materials during the period of this study. On the other hand, eight metalic constituents from the water samples were also assayed, and all metalic ions detected were remarkably low below the legal criteria. However, calcium ion in the water samples from the habitats of P. manchouricus was considerably higher than others. Infection rates of digenetic trematodes in the snails were 6.9% in P. manchouricus and 4.8% in S. libertine, respectively. P. manchouricus snails harboring with thc cercariae of Clonorchis sinensis were only 0.14% among the snails examined, and other trematode cercariae except cercaria of C. sinensis were: furcocercus cercariae, cercaria of Loxogenes liberum type I and II. S. libertine snails parasitized with the cercariae of Metagonimus yokogawai were 1, 5% out of the snails examined, and no cercaria of Paragonimus westermani was found in S. libertine snails in the present study. Digenetic trematode cercariae other than M. yokogawai observed in S. libertina snails were: Cercaria yoshidae (B type) , Cercaria cristata, Cercaria innominatum, Cercaria of Centrocestus formosanus and Cercaria nipponensis.

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Neuronal injury in AIDS dementia: Potential treatment with NMDA open-channel blockers and nitric oxide-related species

  • Lipton, Stuart A.
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1996년도 춘계학술대회
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    • pp.19-29
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    • 1996
  • The neurological manifestations of AIDS include dementia, encountered even in the absence of opportunistic superinfection or malignancy. The AIDS Dementia Complex appears to be associated with several neuropathological abnormalities, including astrogliosis and neuronal injury or loss. How can HIV-1 result in neuronal damage if neurons themselves are only rarely, if ever, infected by the vitus\ulcorner In vitro experiments from several different laboratiories have lent support to the existence of HIV- and immune-related toxins. In one recently defined pathway to neuronal injury, HIV-infected macrophages/microglia as well as macrophages activated by HIV-1 envelope protein gp120 appear to secrete excitants/neurotoxins. These substances may include arachidonic acid, platelet-activating factor, free radicals (NO - and O$_2$), glutamate, quinolinate, cysteine, cytokines (TNF-${\alpha}$, IL1-B, IL-6), and as yet unidentified factors emanating from stimulated macrophages and possibly reactive astrocytes. A final common pathway for newonal suscepubility appears to be operative, similar to that observed in stroke, trauma, epilepsy, and several neurodegenerative diseases, including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves excessive activation of N-methyl-D-aspartate (NMDA) receptor-operated channels, with resultant excessive influx of Ca$\^$2+/ leading to neuronal damage, and thus offers hope for future pharmacological intervention. This chapter reviews two clinically-tolerated NMDA antagonists, memantine and nitroglycerin; (ⅰ) Memantine is an open-channel blocker of the NMDA-associated ion channel and a close congener of the anti-viral and anti-parkinsonian drug amantadine. Memantine blocks the effects of escalating levels of excitotoxins to a greater degree than lower (piysiological) levels of these excitatory amino acids, thus sparing to some extent normal neuronal function. (ⅱ) Niuoglycerin acts at a redox modulatory site of the NMDA receptor/complex to downregulate its activity. The neuroprotective action of nitroglycerin at this site is mediated by n chemical species related to nitric oxide, but in a higher oxidation state, resulting in transfer of an NO group to a critical cysteine on the NMDA receptor. Because of the clinical safety of these drugs, they have the potential for trials in humans. As the structural basis for redox modulation is further elucidated, it may become possible to design even better redox reactive reagents of chinical value. To this end, redox modulatory sites of NMDA receptors have begun to be characterized at a molecular level using site-directed mutagenesis of recombinant subunits (NMDAR1, NMDAR2A-D). Two types of redox modulation can be distinguished. The first type gives rise to a persistent change in the functional activity of the receptor, and we have identified two cysteine residues on the NMDARI subunit (#744 and #798) that are responsible for this action. A second site, presumably also a cysteine(s) because <1 mM N-ethylmaleimide can block its effect in native neurons, underlies the other, more transient redox action. It appears to be at this, as yet unidentified, site on the NMDA receptor that the NO group acts, at least in recombinant receptors.

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Inhibitory Effects of Ginsenoside Metabolites, Compound K and Protopanaxatriol, on $GABA_C$ Receptor-Mediated Ion Currents

  • Lee, Byung-Hwan;Hwang, Sung-Hee;Choi, Sun-Hye;Kim, Hyeon-Joong;Lee, Joon-Hee;Lee, Sang-Mok;Ahn, Yun Gyong;Nah, Seung-Yeol
    • The Korean Journal of Physiology and Pharmacology
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    • 제17권2호
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    • pp.127-132
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    • 2013
  • Ginsenosides, one of the active ingredients of Panax ginseng, show various pharmacological and physiological effects, and they are converted into compound K (CK) or protopanaxatriol (M4) by intestinal microorganisms. CK is a metabolite derived from protopanaxadiol (PD) ginsenosides, whereas M4 is a metabolite derived from protopanaxatriol (PT) ginsenosides. The ${\gamma}$-aminobutyric acid $receptor_C$ ($GABA_C$) is primarily expressed in retinal bipolar cells and several regions of the brain. However, little is known of the effects of ginsenoside metabolites on $GABA_C$ receptor channel activity. In the present study, we examined the effects of CK and M4 on the activity of human recombinant $GABA_C$ receptor (${\rho}$ 1) channels expressed in Xenopus oocytes by using a 2-electrode voltage clamp technique. In oocytes expressing $GABA_C$ receptor cRNA, we found that CK or M4 alone had no effect in oocytes. However, co-application of either CK or M4 with GABA inhibited the GABA-induced inward peak current ($I_{GABA}$). Interestingly, pre-application of M4 inhibited $I_{GABA}$ more potently than CK in a dose- dependent and reversible manner. The half-inhibitory concentration ($IC_{50}$) values of CK and M4 were $52.1{\pm}2.3$ and $45.7{\pm}3.9{\mu}M$, respectively. Inhibition of $I_{GABA}$ by CK and M4 was voltage-independent and non-competitive. This study implies that ginsenoside metabolites may regulate $GABA_C$ receptor channel activity in the brain, including in the eyes.

이가 양이온과 세포막 인산화 반응의 억제제가 Synaptosome에서의 소듐-칼슘 교환이동에 미치는 영향 (Influences of Divalent Cations and Membrane Phosphorylation Inhibitors on $Na^+-Ca^{++}$ Exchange in Synaptosomes)

  • 신용규;이정수;이광수
    • 대한약리학회지
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    • 제24권2호
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    • pp.179-187
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    • 1988
  • 소듐에 의한 칼슘의 유리는 verapamil, TTX, TEA의 영향을 받지 않았다. $100\;{\mu}M\;Cd6{++}$$Zn^{++}$은 소듐에 의한 칼슘 유출을 유의하게 억제하였다. $Cd^{++}$$Ki\;100\;{\mu}M\;Cd6{++}$로써 비상경적으로 소듐-칼슘 교환이동을 억제하였다. $Cd^{++}$은 SH기의 산화를 초래하였으나, $Zn^{++}$은 거의 영향을 나타내지 않았다. $Cd^{++}$$Zn^{++}$$Na^+-Ca^{++}$ ATPase를 효과적으로 억제하였으나 $Ca^{++}-Mg^{++}$ ATPase를 약간 억제시켰다. Carbonyl cyanide chlorophenylhydrazone, 2,4-dinitrophenol과 sodium arsenate는 소듐에 의한 칼슘 유리를 촉진하였다. Dibucaine과 oligomycin은 소듐에 의한 칼슘의 유리를 약간 억제하였으나, 이에 반하여 ouabain은 약간 촉진하였다. 이상의 실험 결과로부터 신경 세포막에서의 소듐-칼슘 교환은 이온 통로를 통하여 이루어지지 않을 것으로 시사되었다. 소듐-칼슘 교환이동은 $Cd^{++}$에 민감하게 억제되고 이 이동기전에 synaptosome막의 SH기가 관여할 것으로 사료되었다. 또한 소듐-칼슘 교환은 세포막 단백질 성분의 인산화 반응 동안에 억압될 것으로 추정되었다.

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Site-selective Photoluminescence Spectroscopy of Er-implanted Wurtzite GaN under Various Annealing Condition

  • Kim, Sangsig;Sung, Man Young;Hong, Jinki;Lee, Moon-Sook
    • Transactions on Electrical and Electronic Materials
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    • 제1권1호
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    • pp.26-31
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    • 2000
  • The ~1540 nm $^4$ $I_{13}$ 2/ longrightarro $w^4$ $I_{15}$ 2/ emissions of E $r^{3+}$ in Er-implanted GaN annealed at temperatures in the 400 to 100$0^{\circ}C$ range were investigated to gain a better understanding of the formation and dissociation processes of the various E $r^{3+}$ sites and the recovery of damage caused by the implantation with increasing annealing temperature ( $T_{A}$).The monotonic increase in the intensity of the broad defect photoluminescence(PL) bands with incresing $T_{A}$ proves that these are stable radiative recombination centers introduced by the implantation and annealing process. Theser centers cannot be attributed to implantation-induced damage that is removed by post-implantation annealing. Selective wavelength pumpling of PL spectra at 6K reveals the existence of at least nine different E $r^{3+}$ sites in this Er-implanted semiconductor. Most pf these E $r^{3+}$ PL centers are attributed to complexed of Er atoms with defects and impurities which are thermally activated at different $T_{A}$. Only one of the nine observed E $r^{3+}$ PL centers can be pumped by direct 4f absorption and this indicates that it is highest concentration E $r^{3+}$ center and it represents most of the optically active E $r^{3+}$ in the implanted sample. The fact that this E $r^{3+}$ center cannot be strongly pumped by above-gap light or broad band below-gap absorption indicates that it is an isolated center, i.e not complexed with defects or impurities, The 4f-pumped P: spectrum appears at annealing temperatures as low as 40$0^{\circ}C$, and although its intensity increase monotonically with increasing $T_{A}$ the wavelengths and linewidths of its characteristic peaks asre unaltered. The observation of this high quality E $r_{3+}$PL spectrum at low annealing temperatures illustrates that the crystalline structure of GaN is not rendered amorphous by the ion implantation. The increase of the PL intensities of the various E $R_{3+}$sites with increasing $T_{A}$is due to the removal of competing nonradiative channels with annealing. with annealing.annealing.

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결정화도에 따른 Li3V2(PO4)3 음극의 전기화학적 특성 (Electrochemical Characteristics of Li3V2(PO4)3 Negative Electrode as a Function of Crystallinity)

  • 구준환;박경진;류지헌;오승모
    • 전기화학회지
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    • 제15권1호
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    • pp.27-34
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    • 2012
  • 열처리 온도를 $600^{\circ}C$$800^{\circ}C$로 다르게 하여 비정질 및 결정질구조의 탄소를 포함하는 $Li_3V_2(PO_4)_3/C$분말을 각각 합성하였으며, 결정성에 따른 리튬 이차전지용 음극으로의 특성을 비교하였다. 결정질 $Li_3V_2(PO_4)_3/C$은 추가반응에 의하여 리튬이 저장되기 때문에 260 mAh $g^{-1}$의 제한된 용량만을 지니고 있음에 비하여, 비정질 $Li_3V_2(PO_4)_3/C$는 3가의 바나듐이 금속상태에 근접할 정도로 가역적으로 반응되어 460 mAh $g^{-1}$의 큰가역용량을 발현함을 확인하였다. 이는 비정질 구조에서 기인하는 특성으로 유연한 구조로 인한 새로운 리튬의 저장공간이 확보되는 것 때문이라 할 수 있다. 또한, 비정질 $Li_3V_2(PO_4)_3/C$는 비정질 구조에 기인하는 선형적인 충방전 곡선을 지니고 있어 정확한 충전심도의 예측이 용이할 뿐만 아니라, 결함구조에서 유발된 리튬이온의 향상된 확산성으로 인하여 우수한 속도 특성도 나타내고 있다.

전리방사선이 세포질 소기관의 미세구조변화와 기전에 미치는 영향 (The Effect of Ionizing Radiation on the Ultrastructural Changes and Mechanism on the Cytoplasmic Organelles)

  • 이무석;이종규;남지호;하태영;임영현;길상형
    • 생명과학회지
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    • 제27권6호
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    • pp.708-725
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    • 2017
  • 전리방사선은 물질과 상호작용하여 원자내의 중성자나 양성자, 궤도전자를 충분히 제거시킬 수 있는 에너지이다. 이와 같은 전리방사선은 DNA이나 세포질 소기관과 세포질의 방사선 분해 생성물을 통해 직접적, 간접적으로 상호작용하여 분자구조를 변화시키는 산화적 대사를 일으킨다. 이러한 전리 현상은 분자수준에서 조직을 손상시키고, 세포 기능을 파괴할 수 있다. 따라서, 전리방사선에 의해 유도된 이온채널과 수송 변형이 보고되고 있다. 이러한 현상이 항상성을 유지하기 위한 생화학적 과정을 무너뜨리면, 유도된 생물학적 변화가 지속되고 후대로 영향을 미친다. 또한, 전리방사선의 영향으로 형성된 활성산소는 세포연접을 통해 인접세포로 퍼져 나갈 수 있다. 방사선량, 선량률, 선질에 따라 이러한 메커니즘이 충분히 방어할 수도 있고 그렇지 않을 수도 있다. 본 총설에서는 방사선생물학의 개념을 뒷받침하는 전리방사선의 세포수준에서 생물학적 효과에 대한 보고서를 간략히 알아보았다. 전리방사선의 생물학적 효과를 잘 이해하면 방사선을 잘 이용할 수 있고, 방사선피폭으로부터 더 나은 방호를 할 수 있을 것이다.