Inhibition of N-type calcium current by cirazoline in rat superior cervical ganglion.

의과학사업단/석사[한글] 성숙한 쥐의 superior cervical ganglion (SCG) 세포에서 신경말단으로부터의 norepinephrine (NE) 방출은 주로 ■2-adrenergic autoreceptor를 통한 칼슘전류 감소에 의해 억제되는 것으로 알려져 왔다. 한편 일부의 imidazoline계 약물 역시 교감신경 말단에서의 NE 방출을 조절하는데, 이때 ■2-autoreceptor가 아닌 다른 수용체를 통하여 그 작용이 발휘되는 것으로 보고되었다. 이들을 imidazoline 수용체라 하는데, 약리적 특성에 기초하여 I1-수용체, I2-수용체, I3-수용체, non-I1,2,3 수용체 등으로 분류된다. 수용체에 대한 리간드의 친화력 연구에 의하면, imidazoline계 약물은 대부분 imidazoline 수용체뿐만 아니라 ■2-autoreceptor에도 친화력을 가지는데 그 중에서 cirazoline은 비교적 non-I1,2,3 수용체에 선택적으로 작용하는 약물로 보고되고 있다. 또한 cirazoline이 교감신경말단에서의 NE 방출을 억제한다는 실험보고도 있다. 그러나 이러한 cirazoline에 의한 NE 방출 억제에 관한 구체적인 기전은 아직 밝혀지지 않고 있다. 본 연구에서는 cirazoline에 의한 SCG 신경세포말단에서의 NE 방출 억제에 관한 기전을 이해하고자 단일 SCG 세포에서 기록되는 전압 의존적 칼슘전류를 NE 방출에 대한 모델로 이용하여, 1) cirazoline이 SCG 세포의 전압 의존적 칼슘전류에 미치는 영향을 조사하고, 2) cirazoline의 칼슘전류에 대한 효과를 매개하는 수용체의 종류를 밝히고, 3) cirazoline에 의한 수용체 활성화에 따른 칼슘전류 조절에 관한 가능한 세포내 기전을 조사하였다. 효소처리로 분리한 단일 SCG 세포에서의 전압 의존적 칼슘 전류는 whole-cell patch clamp 방법을 이용하여 기록하였다. Cirazoline은 NE와 유사하게 가역적이고 농도 의존적으로 칼슘전류를 억제하였다. Cirazoline-유도 칼슘전류 억제는 ■2-autoreceptor를 차단한 상황(rauwolscine 3 ■M 전처치) 하에서도 관찰되었다. 그러나 동일한 상황 하에서 NE-유도 칼슘전류 억제는 일어나지 않았다. 또한 I1-, I2-, I3-수용체 각각의 길항제를 전처치 한 경우에도 cirazoline은 칼슘전류를 억제하였다. 한편 GDP-■-S (2 mM)를 파이펫 내에 넣어 G-단백질을 불활성화 시켰을 때 cirazoline-유도 칼슘전류 억제는 관찰되지 않았다. SCG 세포를 pertussis toxin (PTX)으로 전처치(18 시간) 하였을 경우, cirazoline-유도 칼슘전류 억제(23%)는 PTX-둔감성으로 세포에 rauwolscine (3 ■M) 만을 전처치한 후 관찰된 cirazoline-유도 칼슘전류 억제(33%, PTX-민감성 및 PTX-둔감성)에 비하여 감소하였다. 하지만 PTX 전처치는 NE-유도 칼슘전류 억제를 거의 완전히 반전(reverse)시켰다. 한편 N-형 칼슘통로 차단제인 ■-conotoxin GVIA를 전처치하였을 때 cirazoline-유도 칼슘전류 억제는 관찰되지 않았다. 이상의 결과는 1) SCG 세포에서 cirazoline은 전압 의존적인 N-형 칼슘통로를 차단함으로서 칼슘전류를 억제하며, 2) 이러한 칼슘통로 차단 효과는 ■2-autoreceptor나 I1-, I2-, I3-수용체가 아닌 non-I1,2,3 수용체에 작용하여 이루어지며, 3) 수용체 활성화에 의한 칼슘통로 차단은 PTX-민감성 및 PTX-둔감성 G-단백질을 매개하여 세포질 내 이차전령계의 개입 없이 세포막에 제한된 경로(membrane-delimited pathway)를 통해 직접적으로 칼슘통로에 작용함을 시사한다. [영문] Presynaptic imidazoline receptors that mediate inhibition of norepnephrine (NE) release have first been identified in rabbit cardiovascular tissue. Superior cervical ganglion (SCG) neurons have imidazoline receptors and N-type Ca2+ channels to modulate neurotransmitter release. However, whether inhibitory action of imidazoline receptor activation is associated with N-type Ca2+ channel blockade is unknown. This study was conducted to see if N-type Ca2+ current observed in SCG neurons is modulated by activation of imidazoline receptors. Ca2+ currents were recorded using the whole-cell patch-clamp technique from neurons isolated enzymatically from adult rat SCG. Ca2+ current was evoked by a depolarizing stepping pulse from -80 to 0mV. Cirazoline (30 ■M) decreased the amplitude of Ca2+ current and slowed its rising phase. However, in the presence of alpha-2 antagonist rauwolscine (3 ■M), the cirazoline-induced inhibitory effect on Ca2+ current was decreased and did not show a kinetic slowing suggesting that alpha-2 adrenoceptors were partially activated by cirazoline in SCG neurons. Most of Ca2+ current was inhibited by N-type channel blocker omega-conotoxin. And in the presence of N-type channel blocker(■-conotoxin GVIA) cirazoline could not inhibit the Ca2+ current indicating that cirazoline inhibited the N-type Ca2+ channel. Internal dialysis with solutions containing 2 mM guanosine-5''-O-(2-thiodiphosphate) (GDP-■-S) blocked the Ca2+ current inhibition by NE or cirazoline. Compared with control, the inhibitory effects of cirazoline on Ca2+ current were decreased when SCG neurons were pretreated with pertussis toxin (PTX) for 18 hr. The presynaptic imidazoline receptor effects were mediated by a membrane-delimited pathway, because the modulation was not seen in cell-attached patches when cirazoline was applied to the bath. Taken together, the results suggest that activation of presynaptic imidazoline receptor in SCG neurons reduced N-type Ca2+ currents via a membrane-delimited, both PTX-sensitive and PTX-insensitive G-protein pathway. This imidazoline receptor mediated inhibition of N-type Ca2+ current may play an important role in modulating neurotransmitter release from SCG neurons.ope

종합병원 입원 환자의 낙상 위험 요인 및 낙상 위험도 평가

학위논문 (석사)-- 서울대학교 대학원 : 간호학과, 2012. 2. 최스미.Purpose: The purpose of this study was to identify risk factors and the relationship between fall and fall risk scores of inpatients. Methods: A total 294 patients who were admitted from January 1 to December 31, 2010 participated. One hundred forth seven patients who have experienced fall were matched by gender, age, medical department with 147 patients who have never experienced fall. The fall informations were obtained through electronic medical records and fall reports. Results: The probability of falls was increased by more pain or no more visual disturbances at admission. Patients who have gotten higher fall risk scores at admission were more likely to fall, and the fallers have got higher fall risk scores at time of falling than at admission. Falls occurred most frequently within five days in the patient room. Most fallers were alert and ambulant with some assistance. After falls, most fallers were observed and the additional fall preventive activities were implemented. Conclusion: The findings of this study support the need of using risk assessment tool for predicting fall risk. This finding can be used as a useful resource to develop nursing intervention strategies for fall prevention.Maste

몇 개의 꼬임 사상의 위상 공간에 나타나는 부분적 차단벽에 대 연구

Maste

HPLC를 이용한 광합성색소 분석과 CHEMTAX 프로그램을 이용한 식물플랑크톤 군집조성 연구

22kc

Temporal variaiton of phytoplankton community related to water column structure in the Korea strait

22scopuskc

Coexpression of P2X3 with TRPV1 in the Rat Trigeminal Sensory Nuclei

Trigeminal primary afferents expressing P2X3 or transient receptor potential vanilloid 1 (TRPV1) are involved in the transmission of nociceptive information. In order to characterize P2X3- and TRPV1-immunopositive neurons in the trigeminal ganglion (TG) and trigeminal caudal nucleus (Vc), we performed immunofluorescence experiments using anti- P2X3 and anti-TRPV1 antisera and a morphometric analysis. 77.4% (1,401/1,801) of all the P2X3-postive neurons coexpressed TRPV1 and 51.9% (1,401/2,698) of all the TRPV1- immunopositive neurons also costained for P2X3 in the TG. Immunoreactivity for both P2X3 and TRPV1 were present in medium-sized neurons but not in small- and large-sized neurons. P2X3- and/or TRPV1-immunopositive fibers were observed in the primary afferents and their associated axons in the Vc. These fibers and terminals were distributed in the superficial lamina of Vc: P2X3-immunopositive fibers and terminals were distributed in the lamina I and II, expecially in the inner part of lamina II (lamina IIi), whereas TRPV1-immunopositive ones were densely detected in the lamina I and outer part of lamina II (lamina IIo). Immunopositive fibers and terminals for both P2X3 and TRPV1 were observed on the border between lamina IIi and IIo. These results suggest that terminals coexpressing P2X3 and TRPV1 are involved in specific roles in the transmission and processing of orofacial nociceptive information.2