An ATP-activated nonselective cation channel in guinea pig ventricular myocytes

1995 ◽  
Vol 269 (3) ◽  
pp. H789-H797 ◽  
Author(s):  
K. E. Parker ◽  
A. Scarpa
Keyword(s):  
Guinea Pig ◽  
Chloride Channels ◽  
Cardiac Electrophysiology ◽  
Ventricular Myocytes ◽  
Traumatic Injury ◽  
Reversal Potential ◽  
Extracellular Atp ◽  
Fluctuation Analysis ◽  
Inward Current ◽  
Inwardly Rectifying

Extracellular ATP released from nerves onto vascular smooth muscle or released from damaged tissues during traumatic injury, shock, or ischemia profoundly alters cardiovascular physiology. We have used patch-clamp methods to investigate the effects of extracellular ATP on guinea pig ventricular myocytes because guinea pigs are a commonly used model for the study of cardiac electrophysiology. We have found that ATP activates a rapid, desensitizing, inward current. This inward current is activated by a P2 receptor that does not conform to published receptor subclasses. A concentration of 100 microM ATP activates more current than 100 microM alpha, beta-methyleneadenosine 5'-triphosphate, which in turn activates more current than 100 microM ADP. 2-Methylthioadenosine 5'-triphosphate (2-MeS-ATP) and adenosine 5'-O-(3-thiotriphosphate) are also effective agonists. Adenosine, AMP, guanosine 5'-triphosphate, and uridine 5'-triphosphate are ineffective at 100 microM. The inward conductance has a reversal potential near 0 mV and in ion-substitution experiments was found to be carried through nonselective cation channels rather than chloride channels. The conductance has inwardly rectifying current-voltage (I-V) relations. When ATP is used as the agonist, fluctuation analysis yields an apparent unitary conductance of 0.08 pA at a holding potential of -120 mV with sodium as the main charge-carrying ion. The combination of inwardly rectifying I-V relations, the efficacy of 2-MeS-ATP, and the very low conductance distinguish this conductance from other ATP-activated nonselective channels, including those recently cloned from rat vas deferens and PC-12 cells.

scholarly journals Two ATP-activated conductances in bullfrog atrial cells.

1988 ◽  
Vol 91 (1) ◽  
pp. 1-27 ◽  
Author(s):  
D D Friel ◽  
B P Bean
Keyword(s):  
Ionic Channels ◽  
Extracellular Atp ◽  
Fluctuation Analysis ◽  
Current Fluctuation ◽  
Atrial Cells ◽  
Atp Analogues ◽  
Alpha Beta ◽  
Gamma S ◽  
Inwardly Rectifying ◽  
Current Fluctuation Analysis

Currents activated by extracellular ATP were studied in single voltage-clamped bullfrog atrial cells. Rapid application of ATP elicited currents carried through two different conductance pathways: a rapidly desensitizing conductance reversing near -10 mV, and a maintained, inwardly rectifying conductance reversing near -85 mV. ATP activated the desensitizing component of current with a K 1/2 of approximately 50 microM and the maintained component with a K 1/2 of approximately 10 microM. Both types of current were activated by ATP but not by adenosine, AMP, or ADP. The desensitizing current was selectively inhibited by alpha, beta-methylene ATP, and the maintained, inwardly rectifying current was selectively suppressed by extracellular Cs. The desensitizing component of current was greatly reduced when extracellular Na was replaced by N-methylglucamine, but was slightly augmented when Na was replaced by Cs. GTP, ITP, and UTP were all ineffective in activating the desensitizing current, and of a variety of ATP analogues, only ATP-gamma-S was effective. Addition of EGTA or BAPTA to the intracellular solution did not obviously affect the desensitizing current. Fluctuation analysis of currents through the desensitizing conductance suggested that current is carried through ionic channels with a small (less than pS) unitary conductance.

Electroporation-Induced Inward Current in Voltage-Clamped Guinea Pig Ventricular Myocytes

2010 ◽  
Vol 238 (1-3) ◽  
pp. 69-80 ◽  
Author(s):  
Oksana Dyachok ◽  
Pavel Zhabyeyev ◽  
Terence F. McDonald
Keyword(s):  
Guinea Pig ◽  
Ventricular Myocytes ◽  
Inward Current

Modulation of membrane potential by an acetylcholine-activated potassium current in trout atrial myocytes

2007 ◽  
Vol 292 (1) ◽  
pp. R388-R395 ◽  
Author(s):  
Cristina E. Molina ◽  
Hans Gesser ◽  
Anna Llach ◽  
Lluis Tort ◽  
Leif Hove-Madsen
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Ventricular Myocytes ◽  
Reversal Potential ◽  
Membrane Potentials ◽  
Resting Membrane Potential ◽  
Atrial Myocytes ◽  
Atrial Tissue ◽  
Isolated Cardiac Myocytes ◽  
Inwardly Rectifying

Application of the current-clamp technique in rainbow trout atrial myocytes has yielded resting membrane potentials that are incompatible with normal atrial function. To investigate this paradox, we recorded the whole membrane current ( Im) and compared membrane potentials recorded in isolated cardiac myocytes and multicellular preparations. Atrial tissue and ventricular myocytes had stable resting potentials of −87 ± 2 mV and −83.9 ± 0.4 mV, respectively. In contrast, 50 out of 59 atrial myocytes had unstable depolarized membrane potentials that were sensitive to the holding current. We hypothesized that this is at least partly due to a small slope conductance of Im around the resting membrane potential in atrial myocytes. In accordance with this hypothesis, the slope conductance of Im was about sevenfold smaller in atrial than in ventricular myocytes. Interestingly, ACh increased Im at −120 mV from 4.3 pA/pF to 27 pA/pF with an EC50 of 45 nM in atrial myocytes. Moreover, 3 nM ACh increased the slope conductance of Im fourfold, shifted its reversal potential from −78 ± 3 to −84 ± 3 mV, and stabilized the resting membrane potential at −92 ± 4 mV. ACh also shortened the action potential in both atrial myocytes and tissue, and this effect was antagonized by atropine. When applied alone, atropine prolonged the action potential in atrial tissue but had no effect on membrane potential, action potential, or Im in isolated atrial myocytes. This suggests that ACh-mediated activation of an inwardly rectifying K+ current can modulate the membrane potential in the trout atrial myocytes and stabilize the resting membrane potential.

Depression of delayed outward K+ current by Co2+ in guinea pig ventricular myocytes

1991 ◽  
Vol 261 (1) ◽  
pp. C23-C31 ◽  
Author(s):  
Z. Fan ◽  
M. Hiraoka
Keyword(s):  
Guinea Pig ◽  
Ventricular Myocytes ◽  
Hill Coefficient ◽  
Maximal Response ◽  
Fluctuation Analysis ◽  
Dependent Manner ◽  
Surface Charges ◽  
Patch Clamp Technique ◽  
Voltage Range ◽  
K Current

Effects of Co2+ on the delayed outward K+ current (IK) in guinea pig ventricular myocytes were studied using the whole cell patch-clamp technique. IK was activated by depolarizing voltage pulses positive to -30 mV and reached half-maximal activation at +24 mV. Co2+ shifted the activation curve to a more depolarized voltage range in a concentration-dependent manner, with a Co2+ concentration at which half-maximal response occurs (IC50) of 8 mM and a saturation value of +38 mV. The voltage dependency of IK gatings showed a shift similar to that of activation. In both cases the shift could be explained by screening of surface potential. The density of total negative surface charges sensed by Co2+ was estimated to be 1 e/225 A2. Co2+ also reduced the fully activated IK [IK(full)], and the dose-response curve had a Hill coefficient of 0.5 and an IC50 of 1 mM at 0 mV. Depression of IK(full) was mainly voltage independent. The single-channel unitary current estimated by fluctuation analysis was approximately 0.1 pA at -30 mV either in the absence or presence of Co2+. Therefore, the depression of IK(full) is due to an equivalent reduction in the number of functional channels. It is concluded that Co2+ depressed IK through multiple mechanisms.

scholarly journals Inward current related to contraction in guinea-pig ventricular myocytes.

1987 ◽  
Vol 385 (1) ◽  
pp. 565-589 ◽  
Author(s):  
D Fedida ◽  
D Noble ◽  
Y Shimoni ◽  
A J Spindler
Keyword(s):  
Guinea Pig ◽  
Ventricular Myocytes ◽  
Inward Current

Transient outward current carried by inwardly rectifying K+ channels in guinea pig ventricular myocytes dialyzed with low-K+ solution

2004 ◽  
Vol 287 (5) ◽  
pp. C1396-C1403 ◽  
Author(s):  
Pavel Zhabyeyev ◽  
Tatsuya Asai ◽  
Sergey Missan ◽  
Terence F. McDonald
Keyword(s):  
Guinea Pig ◽  
Ventricular Myocytes ◽  
Outward Current ◽  
Transient Outward Current ◽  
K Channels ◽  
Voltage Gated ◽  
Voltage Gated Channels ◽  
Inwardly Rectifying ◽  
Low K ◽  
External K

There have been periodic reports of nonclassic (4-aminopyridine insensitive) transient outward K+ current in guinea pig ventricular myocytes, with the most recent one describing a novel voltage-gated inwardly rectifying type. In the present study, we have investigated a transient outward current that overlaps inward Ca2+ current ( ICa,L) in myocytes dialyzed with 10 mM K+ solution and superfused with Tyrode’s solution. Although depolarizations from holding potential ( Vhp) −40 to 0 mV elicited relatively small inward ICa,L in these myocytes, removal of external K+ or addition of 0.2 mM Ba2+ more than doubled the amplitude of the current. The basis of the enhancement of ICa,L was the suppression of a large transient outward K+ current. Similar enhancement was observed when Vhp was moved to −80 mV and test depolarizations were preceded by short prepulses to −40 mV. Investigation of the time and voltage properties of the outward K+ transient indicated that it was inwardly rectifying and unlikely to be carried by voltage-gated channels. The outward transient was attenuated in myocytes dialyzed with high-Mg2+ solution, accelerated in myocytes dialyzed with 100 μM spermine solution, and abolished with time in myocytes dialyzed with ATP-free solution. These and other findings suggest that the outward transient is a component of classic “time-independent” inwardly rectifying K+ current.

Activation of potassium channels in renal epithelioid cells (MDCK) by extracellular ATP

1989 ◽  
Vol 256 (5) ◽  
pp. C1016-C1021 ◽  
Author(s):  
F. Friedrich ◽  
H. Weiss ◽  
M. Paulmichl ◽  
F. Lang
Keyword(s):  
Potassium Channels ◽  
Single Channel ◽  
Chloride Transport ◽  
Mdck Cells ◽  
Potassium Conductance ◽  
Reversal Potential ◽  
Extracellular Atp ◽  
Extracellular Calcium ◽  
Open Probability ◽  
Inwardly Rectifying

Extracellular ATP has been shown to stimulate transepithelial chloride transport in confluent Madin-Darby canine kidney (MDCK) cell layers and to enhance potassium conductance in subconfluent MDCK cells. The present study has been performed to test for the effect of extracellular ATP on channel activity in patches from subconfluent MDCK cells. Within 8 s, addition of extracellular ATP (10 mumol/l) leads to a sustained, but fully reversible, appearance of potassium-selective channels in cell-attached patches [increase of open probability from 0.03 +/- 0.02 (n = 10) to 0.50 +/- 0.07 (n = 6)]. With the use of pipettes filled with 145 mmol/l KCl, inwardly rectifying property of the channels is disclosed with a single-channel conductance of 65.7 +/- 3.1 pS (n = 9) at zero potential difference between pipette and bath and with a reversal potential of 75.4 +/- 2.0 mV (n = 5; pipette negative vs. reference in the bath). The open probability of the channels is not significantly modified by altering pipette potential from -50 mV, pipette positive, to 50 mV, pipette negative. At extracellular calcium activities of less than 10 nmol/l, ATP leads to a transient activation of channels. In conclusion, extracellular ATP activates inwardly rectifying potassium channels in the cell membrane of subconfluent MDCK cells. A sustained activation of the channels requires the presence of extracellular calcium and is probably mediated by increases in intracellular calcium.

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