Characteristics of the second inward current in cells isolated from rat ventricular muscle

1983 ◽  
Vol 219 (1217) ◽  
pp. 447-469 ◽  
Keyword(s):  
Single Cells ◽  
External Solution ◽  
Maximum Level ◽  
Charge Carriers ◽  
Ventricular Muscle ◽  
Inward Current ◽  
Adult Rat ◽  
Time To Peak ◽  
Rat Hearts ◽  
Steady Level

The second inward current ( I si ) in single cells isolated from ventricular muscle of adult rat hearts was measured in response to step depolarizations under voltage-clamp conditions. The major ion carrying this current was Ca, and I si was reduced or abolished by Mn, Ni, Cd, nifedipine, nimodipine and D600. Sr and Ba could substitute for Ca as charge carriers, and reduced the rate of apparent inactivation of I si . These effects of Sr and Ba, together with the relation between the steady level of apparent inactivation and membrane potential in Ca containing solution, were taken as evidence that inactivation was at least in part dependent on internal Ca. The reduction of external Na to 11% of normal caused a reduction in peak I si when Ca was present in the external solution, but did not reduce I si when Ca was replaced by Sr. It therefore seems unlikely that Na is a major charge carrier I si under the conditions of our experiments. The time-to-peak and rate of apparent inactivation of I si were faster than in previous studies that used multicellular preparations. Both the kinetics and peak amplitude of I si were markedly dependent on temperature ( Q 10 close to 3). Contraction of the cells, which was monitored optically, was initiated within 3 ms of the peak I si , reached a maximum level after approximately 40–50 ms, and was about 100 ms in duration.

Doxorubicin-induced late cardiotoxicity: delayed impairment of Ca2+-handling mechanisms in the sarcoplasmic reticulum in the rat

2000 ◽  
Vol 78 (4) ◽  
pp. 329-338 ◽  
Author(s):  
Akihito Chugun ◽  
Kyosuke Temma ◽  
Toshifumi Oyamada ◽  
Natsuyo Suzuki ◽  
Yoshinori Kamiya ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Left Atrial ◽  
Force Frequency ◽  
Ventricular Muscle ◽  
Doxorubicin Treatment ◽  
Time To Peak ◽  
Atrial Muscle ◽  
Late Cardiotoxicity ◽  
Cardiac Functions ◽  
Rat Hearts

Doxorubicin treatment causes delayed development of cardiotoxicity. Whether the doxorubicin-induced impairment of cardiac functions reverses or progresses with time after the cessation of the treatment was examined. The rats were injected with doxorubicin (2.5 mg/kg, i.v., once a week for 3 weeks) and sacrificed at 1 (1W), 13 (13W), or 18 (18W) weeks after the final doxorubicin administration. The time to peak of twitch contraction observed at 2-Hz stimulation was not altered in left atrial or ventricular muscle preparations isolated from 1W rats, but it was prolonged in those from 13W and 18W rats. The reduction of the magnitude of postrest contraction and the alteration of force-frequency relationships in left atrial muscle preparations in 1W rats were not significant, but were intensified in the 13W and 18W groups. Alterations in the postrest contraction and the force-frequency relationships in ventricular muscle preparations isolated from doxorubicin-treated rat hearts were weaker, but the pattern of alteration was similar to that observed in left atrial muscle preparations. Caffeine-induced contraction observed in skinned fibers that were isolated from the 1W rats was not altered, but it was reduced in the 18W rats. The Ca2+ sensitivity of contractile proteins was not altered in doxorubicin-treated rat hearts in any of the groups. The Kd values estimated from a [3H]ryanodine binding study were not altered, but the Bmax values were significantly lower in the 13W and 18W groups than those observed in control rats. These results suggest that the dysfunction of the sarcoplasmic reticulum progresses after the completion of doxorubicin treatment and contributes to the doxorubicin-induced late cardiotoxicity.Key words: doxorubicin, late cardiotoxicity, rat heart, sarcoplasmic reticulum.

scholarly journals Calcium feedback and sensitivity regulation in primate rods.

1991 ◽  
Vol 98 (1) ◽  
pp. 95-130 ◽  
Author(s):  
T Tamura ◽  
K Nakatani ◽  
K W Yau
Keyword(s):  
Outer Segment ◽  
Time Course ◽  
Bright Light ◽  
External Solution ◽  
Physiological Solution ◽  
Spatial Homogeneity ◽  
Inward Current ◽  
Time To Peak ◽  
Feedback Model ◽  
Locke Solution

Membrane current was recorded from a single primate rod with a suction pipette while the cell was bath perfused with solutions maintained at a temperature of approximately 38 degrees C. A transient inward current was observed at the onset of bright illumination after briefly exposing the outer segment in darkness to Ringer's (Locke) solution containing 3-isobutyl-1-methylxanthine (IBMX), an inhibitor of cGMP phosphodiesterase. After briefly removing external Na+ from around the outer segment in darkness, a similar current was observed upon Na+ restoration in bright light. By analogy to amphibian rods, this inward current was interpreted to represent the activity of an electrogenic Na(+)-dependent Ca2+ efflux, which under physiological conditions in the light is expected to reduce the free Ca2+ in the outer segment and provide negative feedback (the "Ca2+ feedback") to the phototransduction process. The exchange current had a saturated amplitude of up to approximately 5 pA and a decline time course that appeared to have more than one exponential component. In the absence of the Ca2+ feedback, made possible by removing the Ca2+ influx and efflux at the outer segment using a 0 Na(+)-0 Ca2+ external solution, the response of a rod to a dim flash was two to three times larger and had a longer time to peak than in physiological solution. These changes can be approximately accounted for by a simple model describing the Ca2+ feedback in primate rods. The dark hydrolytic rate for cGMP was estimated to be 1.2 s-1. The incremental hydrolytic rate, beta*(t), activated by one photoisomerization was approximately 0.09 s-1 at its peak, with a time-integrated activity, integral of beta*(t)dt, of approximately 0.033, both numbers being derived assuming spatial homogeneity in the outer segment. Finally, we have found that primate rods adapt to light in much the same way as amphibian and other mammalian rods, such as showing a Weber-Fechner relation between flash sensitivity and background light. The Ca2+ feedback model we have constructed can also explain this feature reasonably well.

Load-Induced Growth Responses in Isolated Adult Rat Hearts

Circulation ◽  
1997 ◽  
Vol 95 (12) ◽  
pp. 2677-2683 ◽  
Author(s):  
Christiane D. Thienelt ◽  
Ellen O. Weinberg ◽  
Jozef Bartunek ◽  
Beverly H. Lorell
Keyword(s):  
Growth Responses ◽  
Adult Rat ◽  
Rat Hearts

scholarly journals Low-voltage activated (LVA) inward current in murine antral smooth muscle cells is an artifact

2021 ◽  
Author(s):  
Ji Yeon Lee ◽  
Haifeng Zheng ◽  
Kenton M. Sanders ◽  
Sang Don Koh
Keyword(s):  
Low Voltage ◽  
External Solution ◽  
Physiological Salt Solution ◽  
Channel Blockers ◽  
Free Solution ◽  
Inward Current ◽  
High K ◽  
Voltage Dependent ◽  
Inward Currents ◽  
Rich Solution

We characterized the two types of voltage-dependent inward currents in murine antral SMC. The HVA and LVA inward currents were identified when cells were bathed in Ca2+-containing physiological salt solution. We examined whether the LVA inward current was due to: 1) T-type Ca2+ channels, 2) Ca2+-activated Cl- channels, 3) non-selective cation channels (NSCC) or 4) voltage-dependent K+ channels with internal Cs+-rich solution. Replacement of external Ca2+ (2 mM) with equimolar Ba2+ increased the amplitude of the HVA current but blocked the LVA current. Nicardipine blocked the HVA current, and in the presence of nicardipine, T-type Ca2+ blockers failed to block LVA. The Cl- channel antagonist had little effect on LVA. Cation-free external solution completely abolished both HVA and LVA. Addition of Ca2+ in cation-free solution restored only HVA currents. Addition of K+ (5 mM) to cation-free solution induced LVA current that reversed at -20 mV. These data suggest that LVA is not due to T-type Ca2+ channels, Ca2+-activated Cl- channels or NSCC. Antral SMC express A-type K+ currents (KA) and delayed rectifying K+ currents (KV) with dialysis of high K+ (140 mM) solution. When cells were exposed to high K+ external solution with dialysis of Cs+-rich solution in the presence of nicardipine, LVA was evoked and reversed at positive potentials. These HK-induced inward currents were blocked by K+ channel blockers, 4-aminopyridine and TEA. In conclusion, LVA inward currents can be generated by K+ influx via KA and KV channels in murine antral SMC when cells were dialyzed with Cs+-rich solution.

scholarly journals Enhanced activity of ventricular Na+-HCO3− cotransport in pressure overload hypertrophy

2007 ◽  
Vol 293 (2) ◽  
pp. H1254-H1264 ◽  
Author(s):  
Taku Yamamoto ◽  
Takeshi Shirayama ◽  
Tomohiko Sakatani ◽  
Tomosaburo Takahashi ◽  
Hideo Tanaka ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Single Cells ◽  
Ischemia Reperfusion ◽  
Pressure Overload ◽  
Pcr Analysis ◽  
Mrna Levels ◽  
Aortic Constriction ◽  
Ph Indicator ◽  
Adult Rat ◽  
Acid Extrusion

The Na+-HCO3− cotransporter (NBC) plays a key role in intracellular pH (pHi) regulation in normal ventricular muscle. However, the state of NBC in nonischemic hypertrophied hearts is unresolved. In this study, we examined functional and molecular properties of NBC in adult rat ventricular myocytes. The cells were enzymatically isolated from both normal and hypertrophied hearts. Ventricular hypertrophy was induced by pressure overload created by suprarenal abdominal aortic constriction of 50% for 7 wk. pHi was measured in single cells using the fluorescent pH indicator 2′,7′-bis(2-carboxyethyl)5-( 6 )carboxyfluorescein. Real-time PCR analysis was used to quantitatively assess expression of NBC-encoding mRNA, including SLC4A4 (encoding electrogenic NBC, NBCe1) and SLC4A7 (electroneutral NBC, NBCn1). Our results demonstrate that: 1) mRNA levels of both the electrogenic NBCe1 (SLC4A4) and electroneutral NBCn1 (SLC4A7) forms of NBC were increased by aortic constriction, 2) the onset of NBC upregulation occurred within 3 days after constriction, 3) normal and hypertrophied ventricles displayed regional differences in NBC expression, 4) acid extrusion via NBC ( JNBC) was increased significantly in hypertrophied myocytes, 5) although acid extrusion via Na+/H+ exchange was also increased in hypertrophied myocytes, the relative enhancement of JNBC was larger, 6) membrane depolarization markedly increased JNBC in hypertrophied myocytes, and 7) losartan, an ANG II AT1 receptor antagonist, significantly attenuated the upregulation of both NBCs induced by 3 wk of aortic constriction. Enhanced NBC activity during hypertrophic development provides a mechanism for intracellular Na+ overload, which may render the ventricles more vulnerable to Ca2+ overload during ischemia-reperfusion.

scholarly journals Glycolytic inhibition causes spontaneous ventricular fibrillation in aged hearts

2011 ◽  
Vol 301 (1) ◽  
pp. H180-H191 ◽  
Author(s):  
Norishige Morita ◽  
Jong-Hwan Lee ◽  
Aneesh Bapat ◽  
Michael C. Fishbein ◽  
William J. Mandel ◽  
...  
Keyword(s):  
Ventricular Fibrillation ◽  
Connexin 43 ◽  
Left Ventricular ◽  
Triggered Activity ◽  
Adult Rat ◽  
Rat Hearts ◽  
Intracellular Calcium Ion ◽  
Dependent Protein ◽  
Isolated Cardiac Myocytes ◽  
Delayed Afterdepolarizations

Selective glycolytic inhibition (GI) promotes electromechanical alternans and triggered beats in isolated cardiac myocytes. We sought to determine whether GI promotes triggered activity by early afterdepolarization (EAD) or delayed afterdepolarizations in intact hearts isolated from adult and aged rats. Dual voltage and intracellular calcium ion (Cai2+) fluorescent optical maps and single cell glass microelectrode recordings were made from the left ventricular (LV) epicardium of isolated Langendorff-perfused adult (∼4 mo) and aged (∼24 mo) rat hearts. GI was induced by replacing glucose with 10 mM pyruvate in oxygenated Tyrode's. Within 20 min, GI slowed Cai2+ transient decline rate and shortened action potential duration in both groups. These changes were associated with ventricular fibrillation (VF) in the aged hearts (64 out of 66) but not in adult hearts (0 out of 18; P < 0.001). VF was preceded by a transient period of focal ventricular tachycardia caused by EAD-mediated triggered activity leading to VF within seconds. The VF was suppressed by the ATP-sensitive K (KATP) channel blocker glibenclamide (1 μM) but not (0 out of 7) by mitochondrial KATP block. The Ca-calmodulin-dependent protein kinase II (CaMKII) blocker KN-93 (1 μM) prevented GI-mediated VF ( P < 0.05). Block of Na-Ca exchanger (NCX) by SEA0400 (2 μM) prevented GI-mediated VF (3 out of 6), provided significant bradycardia did not occur. Aged hearts had significantly greater LV fibrosis and reduced connexin 43 than adult hearts ( P < 0.05). We conclude that in aged fibrotic unlike in adult rat hearts, GI promotes EADs, triggered activity, and VF by activation of KATP channels CaMKII and NCX.

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