• 대한약리학회지
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• 제32권2호
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• pp.189-199
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• 1996

Myocardial ${\alpha}_1-adrenoceptors$ have been shown to mediate a biphaslc inotropic response that was characterized by a transient decline followed by a sustained increasing phase in guinea pig ventricular muscle. Recently one group reported that an ${\alpha}_1-adrenoceptors-induced$ intracellular $Na^+$ decrease is linked to fast $Na^+$ channel inhibition and another group reported that it is linked to $Na^+$-$K^+$ pump activation by ${\alpha}_{1b}-adrenoceptors$. But until now, its mechanism is not clear. Therefore, to see whether the $Na^+$channel or $Na^+-K^+$ pump is related to a decrease in intracellular $Na^+$ activity and/or the negative inotropic response, and which ${\alpha}_1-adrenoceptor$ subtype was involved in the decrease in intracellular $Na^+$activity by phenylephrine, we used conventional and sodium selective microelectrodes, and tension transducer to determine the effects of ${\alpha}_1-adrenergic$ stimulation on membrane potential, intracellular $Na^+$ activity, and twitch force in guinea pig ventricular muscles. $10^{-5}$ M Phenylephrine produced a slight hyperpolarization of the diastolic membrane potential, a decrease or increase in $a_N^i_a$, and a biphasic inotropic response. The negative inotropic response accompanied by a decrease in intracellular $Na^+$activity, whereas in muscles showing a remarkable positive inotropic response without initial negative inotropic effect was accompanied by an increase in intracellular $Na^+$ activity. The decrease in intracellular $Na^+$ activity was apparently inhibited by WB4101, an antagonist of the ${\alpha}_{1a}-adrenoceptors$. The decrease in intracellular $Na^+$ activity caused by phenylephrine was not abolished or reduced by a block of the fast $Na^+$ channels. $V_{max}$ also was not affected by phenylephrine. Phenylephrine produced an increase in intracellular $Na^+$ activity in the presence of a high concentration of extracellular $Ca^{2+}$ (in quiescent muscle) or phorbol dibutyrate, a protein kinase C activator(in beating muscle). These suggest that the ${\alpha}_{1a}-adrenoceptors-mediated$ decrease in intracellular $Na^+$ activity may be related to the protein kinase C.

• Molecules and Cells
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• 제20권3호
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• pp.315-324
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• 2005

Pain is an unpleasant sensation experienced when tissues are damaged. Thus, pain sensation in some way protects body from imminent threat or injury. Peripheral sensory nerves innervated to peripheral tissues initially respond to multiple forms of noxious or strong stimuli, such as heat, mechanical and chemical stimuli. In response to these stimuli, electrical signals for conducting the nociceptive neural signals through axons are generated. These action potentials are then conveyed to specific areas in the spinal cord and in the brain. Sensory afferent fibers are heterogeneous in many aspects. For example, sensory nerves are classified as $A{\alpha}$, $-{\beta}$, $-{\delta}$ and C-fibers according to their diameter and degree of myelination. It is widely accepted that small sensory fibers tend to respond to vigorous or noxious stimuli and related to nociception. Thus these fibers are specifically called nociceptors. Most of nociceptors respond to noxious mechanical stimuli and heat. In addition, these sensory fibers also respond to chemical stimuli [Davis et al. (1993)] such as capsaicin. Thus, nociceptors are considered polymodal. Recent advance in research on ion channels in sensory neurons reveals molecular mechanisms underlying how various types of stimuli can be transduced to neural signals transmitted to the brain for pain perception. In particular, electrophysiological studies on ion channels characterize biophysical properties of ion channels in sensory neurons. Furthermore, molecular biology leads to identification of genetic structures as well as molecular properties of ion channels in sensory neurons. These ion channels are expressed in axon terminals as well as in cell soma. When these channels are activated, inward currents or outward currents are generated, which will lead to depolarization or hyperpolarization of the membrane causing increased or decreased excitability of sensory neurons. In order to depolarize the membrane of nerve terminals, either inward currents should be generated or outward currents should be inhibited. So far, many cationic channels that are responsible for the excitation of sensory neurons are introduced recently. Activation of these channels in sensory neurons is evidently critical to the generation of nociceptive signals. The main channels responsible for inward membrane currents in nociceptors are voltage-activated sodium and calcium channels, while outward current is carried mainly by potassium ions. In addition, activation of non-selective cation channels is also responsible for the excitation of sensory neurons. Thus, excitability of neurons can be controlled by regulating expression or by modulating activity of these channels.

• The Korean Journal of Physiology
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• 제14권2호
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• pp.7-16
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• 1980

The effects of various inotropic interventions on the shape of the steady state length tension relation and the length-dependent activation process in cardiac muscle were studied. The influence of inotropic interventions upon the action potential was also observed. The range of varying muscle length was from the optimal length$(l_{max})$, where the active tension production is maximal, to 0.85 $l_{max}$. Changes in stimulus frequency or in external bathing Ca concentration constituted the inotropic interventions in this experiment. The papillary muscles were isolated from the rabbit right ventricles and perfused with $HCO-_3\;-buffered$ normal Tyrode solution which was aerated with $3%\;CO_2-97%\;O_2$ mixed gas and kept at $35^{\circ}C$. Resting Passive tension at $l_{max}$ was approximately 30% of the total tension and appeared from the muscle length of 0.90 $l_{max}$. The effect of stimulus frequency on the steady state level of developed tension was: As the stimulus frequency was increased from 0.1 to 0.5 Hz, there was little change in developed tension. As the frequency was increased further, to a value of about 3 Hz, tension increased steeply. Further increase of the frequency to 5 Hz had little additional effect on the developed tension. The length-tension curves for isometric peak tension became more steeper with the degree of potentiation by inotropic interventions. The relative steepness of the normalized length-tension curves where tension production was expressed as a percentage of maximal tension developed at $l_{max}$, varied inversely with the level of inotropic state and these curves were not superimposable one another. Thus at the stimulus frequency of 2 Hz or at the external Ca concentration of 8 mM, the relative decline in the developed tension for a given change in muscle length was considerably less than the decline observed at the frequency of 0.5 Hz or at the concentration of 2 mM Ca. Action potential duration was prolonged significantly as the frequency increased from 0.2 to 2 Hz, and this change in action potential duration was not observable on the changes in muscle length. There was a tendency of the hyperpolarization of membrane potential when the muscle length was shortened from $l_{max}$ to 0.95 $l_{max}$. These results support the hypothesis that there is a length-dependence of the activation process.

• 대한약리학회지
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• 제31권1호
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• pp.39-51
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• 1995

갑상선 기능 항진증 심장에서의 ${\beta}-adrenoceptor$의 역할은 잘 알려져 있으나 ${\alpha}-adrenoceptor$에 대해서는 알려져 있지 않은 바, 저자 등은 갑상선 기능 항진증 기니픽 심장의 유두근에서 일반 미세 전극과 이온-선택적 미세 전극을 이용하여 세포내 $Na^+$과 $H^+$ 활성도에 대한 phenylephrine의 영향을 연구하였다. Phenylephrine ($10^{-5}$ 또는 $3{\times}10^{-5}M$)에 의한 ${\alpha}_1-adrenoceptor$ 자극은 다양한 활동전위의 변동, 수축기 막전위의 과분극 ($1.5{\pm}0.1mM$), 세포내 활성도 증가 ($0.4{\pm}0.15mM$), 현저한 수축력 증가 ($220{\pm}15%$) 그리고 세포내 pH의 증가 ($0.06{\pm}0.002\;unit$)를 일으켰고, 이와 같은 변동이 prazosin과 atenolol에 의해 차단되었다. 그래서 이들 효과가 ${\alpha}_1-adrenoceptor$를 경유함을 알 수 있었고, 역시, 세포내 $Na^+$ 활성도와 수축력 증가 효과가 $Na^{+}-H^{+}$ 교환기 억제제인 ethylisopropylamiloride로 차단됨으로 보아 ${\alpha}_1-adrenoceptor$ 자극은 $Na^{+}-H^{+}$ 교환기를 자극하여 세포내 $a^{i}_{Na}$와 pH를 증가시킴을 시사한다. 이는 ${\alpha}_1-adrenoceptor$ 자극에 의한 세포내 $Na^+$감소와 초기 수축력 감소 효과를 나타내는 정상 기니픽 심장과는 매우 다른 결과로 갑상선 기능 항진증 심장에서 ${\alpha}_1-adrenoceptor$는 매우 중요한 기능을 갖고 있음을 의미한다.

• 대한약리학회지
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• 제29권2호
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• pp.263-274
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• 1993

$K^+$통로는 기도 평활근 세포에 존재하며 이들 통로가 활성화되면 평활근의 과분극의 결과 이완작용이 나타난다. $K^+$통로의 이런 효과는 과민반응과 천식 치료에 응용될 수 있으므로 우리는 $K^+$통로 개방제인 cromakalim (BRL34915, CK)이 $IgG_1$ 항체로 감작시킨 기도 및 폐조직으로 부터 유리되는 매개체 유리에 미치는 영향을 조사하였다. 피동적으로 감작된 두 조직은 $2{\times}10^{-6}\;M$의 CK로 30분동안 superfusion시킨 후 CK와 항원 (Ox-HSA) 0.1 mg/ml로 자극하였다. 또한 비만세포를 이용하여 CK의 효과를 조사하였다. 해명 폐조직 비만세포는 효소에 의한 digestion method (monodispersed; 미분리 정제), count current elutriation에 의한 방법(partially purified; 부분분리정제), 그리고 discontinuous Percoll방법(highly purified; 순수분리정제)에 의해 순수 분리되었다. CK로 전처치한후, 피동적으로 감작된 비만세포는 OA와 CaI의 여러 농도에 의해 자극되었다. 유리된 Hist은 spectrophotofluorometry에 의해, LT는 면역방사법에 의해 측정되었다. CK 전처치는 $IgG_1$ 감작후 항원에 의해 자극된 기도 조직에서 Hist 유리량을 35%까지, LT 유리량은 40%까지 감소시켰으나 기도 평활근 수축력에는 반응을 나타내지 못하였다. 항원 유도 폐조직에 있어서 CK전처치는 Hist유리량을 25%까지 감소시켰으나 LT 유리에는 미약한 감소를 나타내었다. 해명의 미분리정제, 부분분리정제, 그리고 순수 분리 정제된 비만세포로부터 Hist과 LT은 면역자극(OA)이나 비면역자극(CaI)에 의해 농도 의존적으로 유리되었다. 비만세포에서 유리된 LT는 5-lipoxygenase억제제인 A64077에 의해서 억제됨이 확인되었다. CK전처치는 OA유도 및 CaI유도 해명 폐조직 비만세포에서 Hist과 LT 유리량을 20%까지 감소시켰다. $IgG_1$ 감작후 Ox-HSA유도 기도 평활근 조직이나 혹은 OA유도 및 CaI유도 비만세포에서 Hist과 LT유리에 미치는 CK의 억제효과는 TEA와 GBC에 의해 완전히 봉쇄되었다. 이상의 결과에서 폐조직 비만세포는 LT를 유리할 수 있는 세포로 간주되며, 기도 평활근 이완제로 알려져 있는 CK은 특수 항원 유도 기도 평활근조직에서 매개체 유리를 부분적으로 억제하며, CK은 또한 OA유도 및 CaI로 유도된 순수분리 정제된 비만세포에서 매개체 유리를 부분적으로 억제하는 것으로 보아 비만세포가 활성화시 야기되는 여러 생화학적 현상중에서 미약하나마 $K{^+}$통로가 관여할 것으로 사료된다.

• 대한핵의학회지
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• 제30권4호
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• pp.507-515
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• 1996

1) 강력한 $K^+$ 통로개방제인 pinacidil은 투여한 pinacidil의 농도, T1-201의 방사능양, 실험에 사용된 심근세포 수에 따라 차이는 있었지만 배양된 심근세포의 T1-201섭취를 1.6-2.5배 감소시켰고, 심근내로 유입시킨 T1-201의 세포외로의 배출을 1.6-3.1배 증가시켰다. Pinacidil의 T1-201의 세포내로의 섭취억제는 세포내로 유입되는 T1-201의 세포 내에서의 저류가 억제되어 일어났을 것으로 추측된다. 2) 생쥐체내에 주사한 pinacidil의 효과는 실험관내의 심근세포의 변화처럼 뚜렸하지는 않았지만 T1-201을 주사한 생쥐에서 10분 이후 pinacidil의 정맥주사한 경우에는 혈액과 간장의 방사능치는 치료하지 않은 군보다 약간 높았고, 신장과 심장의 방사능치는 약간 낮은 경향을 보였다. 이상의 배양된 심근세포와 생쥐체내 실험의 연구결과는 항고혈압약제나, 항협심증약, 기관지천식 치료제로 사용되는 $K^+$통로개방제는 심근내로의 T1-201 축적을 억제하고 배출을 촉진시켜. T1-201 심근관류스캔의 판독에 영향을 미칠 수 있을 수 있을 것으로 추측된다.