• Title/Summary/Keyword: Calcium current

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Effects of Bradykinin on Intracellular Calcium Transients in Cardiac Myocytes

  • Park, Choon-Ok;Kim, Yang-Mi;Han, Jae-Hee;Allen, David G.;Hong, Seong-Geun
    • The Korean Journal of Physiology and Pharmacology
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    • v.3 no.6
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    • pp.615-621
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    • 1999
  • In spite many evidences has supported the cardioprotective effect of bradykinin, its direct effects at the cell level are still under question. We investigated the both effects of bradykinin (BK) on $Ca^{2+}-related$ ionic currents using whole cell voltage clamp technique in rabbit cardiomyocytes and on the intracellular $Ca^{2+}$ transient using calcium sensitive fluorescence dye, indo-1AM. Simultaneously with recording intracellular $Ca^{2+}$ transients, cell contractility was estimated from the changes in length of the electrical stimulated rat cardiac myocytes. L-type $Ca^{2+}$ current decreased by bradykinin at the entire voltage range. Inward tail current increased initially up to its maximum about 4 min after exposing myocytes to BK, and then gradually decreased again by further exposure to BK. This tail current decreased remarkably at washing BK off but slowly recovered ca. 20 min later. The change in cell contractility was similar to that in tail current showing initial increase followed by gradual decrease. Removal of BK brought remarkable decrease in contractility, which was recovered $15{\sim}20$ min after cessation of electrical stimulation. Bradykinin increased $Ca^{2+}$ transient initially but after some time $Ca^{2+}$ transient also decreased coincidentally with contractility. From these results, it is suggested that bradykinin exerts directly its cardioprotective effect on the single myocytes by decreasing the intracellular $Ca^{2+}$ level followed by an initial increase in $Ca^{2+}$ transient.

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The Effect of Carbon Monoxide on L-type Calcium Channel Currents in Human Intestinal Smooth Muscle Cells

  • Lim, In-Ja
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.6
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    • pp.357-362
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    • 2003
  • Carbon monoxide (CO) is low molecular weight oxide gas that is endogenously produced under physiological conditions and interacts with another gas, nitric oxide (NO), to act as a gastrointestinal messenger. The aim of this study was to determine the effects of exogenous CO on L-type calcium channel currents of human jejunal circular smooth muscle cells. Cells were voltage clamped with 10 mM barium ($Ba^{2+}$) as the charge carrier, and CO was directly applied into the bath to avoid perfusion induced effects on the recorded currents. 0.2% CO was increased barium current ($I_{Ba}$) by $15{\pm}2$% ($mean{\pm}S.E.$, p<0.01, n=11) in the cells. To determine if the effects of CO on barium current were mediated through the cGMP pathway, cells were pretreated with 1-H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, $10{mu}M$), a soluble guanylyl cyclase inhibitor, and exogenous CO (0.2%) had no effect on barium currents in the presence of ODQ ($2{\pm}1$% increase, n=6, p>0.05). CO mediates inhibitory neurotransmission through the nitric oxide pathway. Therefore, to determine if the effects of CO on L-calcium channels were also mediated through NO, cells were incubated with $N^G-nitro-L-arginine$ (L-NNA, 1 mM), a nitric oxide synthase inhibitor. After L-NNA pretreatment, 0.2 % CO did not increase barium current ($4{\pm}2$% increase, n=6, p>0.05). NO donor, SNAP ($20{\mu}M$) increased barium current by $13{\pm}2$% (n=6, p<0.05) in human jejunal smooth muscle cells. These data suggest that CO activates L-type calcium channels through NO/cGMP dependant mechanism.

Electrophysiological Properties of the Neurons Dissociated from the Nucleus Raphe Magnus in Postnatal Rats (흰쥐의 Nucleus Raphe Magnus로부터 분리된 신경세포의 전기생리학적 성질)

  • Nam Sang-Chae;Lim Won-Il;Cho Sa-Sun;Kim Jun
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.3
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    • pp.233-240
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    • 1997
  • Neurons in the nucleus raphe magnus are involved in descending modulation of nociceptive transmission. In this study, we attempted to investigate electrophysiological properties of the NRM neurons dissociated from the postnatal rat medulla. The NRM neurons in the coronal slices of and the dissociated neurons from the postnatal rat medullae were immunohistochemically identified using antibody against serotonin. Relatively small number of neurons were positively stained in both preparations. The positively stained neurons displayed large cell body with double or multiple neurites. Using whole-cell patch clamp configuration ionic currents were recorded from the dissociated NRM-like neurons selected by criteria such as size and shape of cell body and cell population. Two types, high- and low-threshold, of voltage-dependent calcium currents were recorded from the dissociated NRM-like neurons. Some neurons displayed both types of calcium currents, whereas others displayed only high-threshold calcium current. Voltage-dependent potassium currents were also recorded from the dissociated NRM neurons. Some neurons displayed both transient outward and delayed rectifier currents but others showed only delayed rectifier current. These results suggest that there are at least two types of calcium currents and two types of potassium currents in the dissociated NRM neurons.

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Inactivation of N-Type Calcium Current in Rat Sympathetic Neurons

  • Goo, Yong-Sook;Keith S. Elmslie
    • Proceedings of the Korean Biophysical Society Conference
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    • 1999.06a
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    • pp.52-52
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    • 1999
  • Inactivation of N-type calcium current has been reported to be voltage dependent (Jones & Marks, 1989) and $Ca^{2+}$ dependent(Cox & Dunlap, 1994). We examined inactivation by recording currents from the same cell both in [B $a^{2+}$]$_{o}$ and [C $a^{2+}$]$_{o}$ in rat sympathetic neurons. With 11 mM internal EGTA, fractional inactivation[l-(current amplitude at the end of 5 sec pulse/peak current amplitude [1-(current amplitude at the end of 5 sec pulse/peak current amplitude)] was larger in $Ca^{2+}$(0.80$\pm$0.07) than in $Ba^{2+}$(0.69$\pm$0.10)(n=31, p<0.001), but the current traces were nicely fitted with two exponential components both in $Ba^{2+}$ and $Ca^{2+}$.(omitted)ted)ted)

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EFFECTS OF DENTAL THERAPEUTIC AGENTS ON THE RESPONSE OF THE PULP NERVE (치과치료용 약물이 치수신경의 반응에 미치는 영향)

  • Kwon, Oh-Yang;Yoon, Soo-Han;Lee, Jong-Heun
    • Restorative Dentistry and Endodontics
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    • v.15 no.1
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    • pp.1-15
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    • 1990
  • The aim of this study was to investigate the effect of dental therapeutic agent on conduction velocity and threshold current of intradental A- and C-fibers in the cat. Inferior alveolar nerve of cat anesthetized with sodium pentobarbital was exposed and dissected until response of functional single pulp nerve until could be evoked by monopolar electrical stimulation of the crown of the lower left canine teeth. 10ms rectangular pulse was used to determine the threshold current and 1ms rectangular pulse was used to determine conduction velocity. After application of calcium chloride (1, 2, 6M), calcium hydroxide mixed with saline, potassium chloride (0.2, 0.8, 1.6M), eugenol, zinc oxide eugenol to the cavity on the labial surface, conduction velocity and threshold current of single pulp nerve unit were compared with the control. In 10 cats, 24 $A{\delta}$- and 11 C- pulp nerve units were recorded. The mean conduction velocities of $A{\delta}$- and C-fibers were 7.5m/sec (SD=5.8) and 1.2m/sec (SD=0.4), respectively. The mean threshold current was $12.3{\mu}A$ (SD=5.3) for $A{\delta}$-fibers and $24.9{\mu}A$ (SD=8.1) for C-fibers. 1, 2, 6M calcium chloride caused decrease of conduction velocity and remarkable increase of threshold current in $A{\delta}$- and C-fibers. The effect of calcium hydroxide mixed with saline was similar but smaller than calcium chloride solution. 0.2M potassium chloride had insignificant effect. In 0.8M potassium chloride, the threshold current was increased although conduction velocity was not affected. In 1.6M potassium chloride, the threshold current was increased and the conduction velocity was slowed down. Spontaneous activity was recorded frequently for first 5 min but gradually reduced both in $A{\delta}$- and C-fibers. Eugenol had irreversible effect on pulp nerve in that initially there were not certain changes in the conduction velocity and threshold current of $A{\delta}$- and C-fibers, but the responses to electrical stimulation were abruptly disappeared after sustained application and were not recovered. Contrary to eugenol, zinc oxide eugenol did not caused significant increase of the threhold current and caused time dependent decrease of the conduction velocity, and did not show any irreversible change.

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Presenilin Modulates Calcium-permeant, Magnesium-Nucleotide regulated channel, I(MgNUM)

  • Shin, Sun-Young;Jeong, Soon-Youn;Uhm, Dae-Yong;Sungkwon Chung
    • Proceedings of the Korean Biophysical Society Conference
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    • 2003.06a
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    • pp.47-47
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    • 2003
  • The presenilin 1 (PS1) or PS2 is an essential component of the ${\gamma}$-secretase complex, which mediates the intramembrane proteolysis of selected type-I membrane, including the ${\beta}$-amyloid precursor protein (APP) to yield A${\beta}$. Familial Alzheimer's disease (FAD)-associated mutations in presenilins give rise to an increased production of a highly amyloidogenic A${\beta}$42. In addition to their well-documented proteolytic function, the presenilins play a role in calcium signaling. We have previously reported that presenilin FAD mutations cause highly consistent alterations in intracellular calcium signaling pathways, which include deficits in capacitative calcium entry (CCE), the refilling mechanism for depleted internal calcium stores. However, molecular basis for the presenilin-mediated modulation of CCE remains to be elucidated. In the present study, whole-cell patch clamp method was used to identify a specific calcium-permeable ion channel current(s) that is responsible for the CCE deficits associated with FAD-linked PS1 mutants. Unexpectedly, both voltage-activated and conventional store depletion-activated calcium currents I(CRAC), were absent in HEK293 cells, which were stably transfected either with wild-type or FAD mutant (L286V, M146L, and delta E9) forms of PS1. Recently, magnesium-nucleotide-regulated metal cation current, or I(MagNum), has been described and appears to share many common properties with I(CRAC) including calcium permeability and inhibitor sensitivity (e.g. 2-APB). We have detected I(MagNum) in all 293 cells tested. Interestingly, FAD mutant 293 cells developed only about half of currents compared to PS1 wild type cells.

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Relaxant Effect of Spermidine on Acethylcholine and High $K^+$-induced Gastric Contractions of Guinea-Pig

  • Kim, Young-Chul;Sim, Jae-Hoon;Choi, Woong;Kim, Chan-Hyung;You, Ra-Young;Xu, Wen-Xie;Lee, Sang-Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.12 no.2
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    • pp.59-64
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    • 2008
  • In our previous study, we found that spermine and putrescine inhibited spontaneous and acetylcholine (ACh)-induced contractions of guinea-pig stomach via inhibition of L-type voltage- dependent calcium current ($VDCC_L$). In this study, we also studied the effect of spermidine on mechanical contractions and calcium channel current ($I_{Ba}$), and then compared its effects to those by spermine and putrescine. Spermidine inhibited spontaneous contraction of the gastric smooth muscle in a concentration-dependent manner ($IC_{50}=1.1{\pm}0.11mM$). Relationship between inhibition of contraction and calcium current by spermidine was studied using 50 mM high $K^+$-induced contraction: Spermidine (5 mM) significantly reduced high $K^+$ (50 mM)-induced contraction to 37${\pm}$4.7% of the control (p<0.05), and inhibitory effect of spermidine on $I_{Ba}$ was also observed at a wide range of test potential in current/voltage (I/V) relationship. Pre- and post-application of spermidine (5 mM) also significantly inhibited carbachol (CCh) and ACh-induced initial and phasic contractions. Finally, caffeine (10 mM)-induced contraction which is activated by $Ca^{2+}$-induced $Ca^{2+}$ release (CICR), was also inhibited by pretreatment of spermidine (5 mM). These findings suggest that spermidine inhibits spontaneous and CCh-induced contraction via inhibition of $VDCC_L$ and $Ca^{2+}$ releasing mechanism in guinea-pig stomach.

Inactivation of N-Type Calcium Current in Rat Sympathetic Neurons

  • Lee, Mi-Sun;Goo, Yong-Sook
    • Proceedings of the Korean Biophysical Society Conference
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    • 2001.06a
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    • pp.26-26
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    • 2001
  • Inactivation of N-type calcium current has been reported to be both voltage dependent and Ca$\^$2+/ dependent. We have investigated the effects of Ba$\^$2+/ and Ca$\^$2+/ on N-channel inactivation in rat superior cervical ganglion neurons using the whole cell configuration of patch clamp technique. Inactivation was larger in Ca$\^$2+/ than in Ba$\^$2+/ even with 20 mM BAPTA.(omitted)

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Isoquinolines: Are they possible candidate for $Ca^{2+}$ blockers\ulcorner

  • 장기철;윤용진;조수동;정원석
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.217-217
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    • 1994
  • Calcium entry blockers, capable of inhibiting transmembrane influx of extracellular calcium through specific calcium channels, are useful drugs in the treatment of angina pectoris, hypertension, cardiac arrythmia, and various cardiovascular disorders. Compounds having isoquinoline structures have recently been reported to possess calcium antagonistic action. Therefore, in the present study, we have attempted to synthesize some isoquinoline and related compound.; in order to search for potentially effective chemicals acting on cardiovascular system, and evaluated their pharmacological properties focusing on calcium antagonistic actions. Almost all of the compounds so far synthesized, had inhibitory action against phenylephrine or high potassium-induced contraction in vascular smooth muscle with different degrees of potencies depending on their structures, However, some of tetrahydroisoquinoline analogs showed directly inhibit calcium current in isolated rabbit cardiac myocytes examined by patch clamp techniques. The pharmacological properties of these compounds need more intensive investigation as to whether these chemicals may have developed as a new cardiovascular active drugs. Therefore, we are now under investigation of the mechanism of action of these compounds.

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Determining attitudinal and behavioral factors concerning milk and dairy intake and their association with calcium intake in college students

  • Rose, Angela M.;Williams, Rachel A.;Rengers, Brooke;Kennel, Julie A.;Gunther, Carolyn
    • Nutrition Research and Practice
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    • v.12 no.2
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    • pp.143-148
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    • 2018
  • BACKGROUND/OBJECTIVES: Average intake of calcium among college students is below the recommended intake, and knowledge surrounding the attitudinal and behavioral factors that influence milk and dairy intake, a primary food source of calcium, is limited. The purpose of this study was to evaluate college students' attitudes and behaviors concerning milk and dairy consumption and their association with calcium intake. SUBJECTS/METHODS: Participants were 1,730 undergraduate students who completed an online survey (SurveyMonkey) as part of baseline data collection for a social marketing dairy campaign. The online survey assessed attitudes and behaviors concerning milk and dairy intake, and calcium intake. Questions about milk- and dairy-related attitudes and behaviors were grouped into 14 factors using factor analysis. Predictors of calcium intake were then evaluated. RESULTS: Median calcium intake across all participants was 928.6 mg/day, with males consuming higher calcium intakes than females (P < 0.001). Adjusted for gender, calcium intakes were most strongly (and positively) correlated with associating milk with specific eating occasions and availability (i.e., storing calcium-rich foods in one's dorm or apartment) (both P < 0.001). Other correlates of calcium intake included: positive-viewing milk as healthy (P = 0.039), having family members who drink milk) (P = 0.039), and taking calcium supplements (P = 0.056); and negative-parent rules concerning milk (P = 0.031) and viewing milk in dining halls negatively (P = 0.05). CONCLUSIONS: Calcium intakes among college students enrolled in the current study was below the recommended dietary allowance of 1,000 mg/day, reinforcing the need for dietary interventions in this target population, especially females. Practitioners and researchers should consider the factors found here to impact calcium intake, particularly associating milk with specific eating occasions (e.g., milk with breakfast) and having calcium-rich foods available in the dorm room or apartment, as intervention strategies in future efforts aimed at promoting milk and dairy foods and beverages for improved calcium intake in college students.