This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mitsuiye, T. Articles by Noma, A. Search for Related Content PubMed PubMed Citation Articles by Mitsuiye, T. Articles by Noma, A. Related Collections Electrophysiology Pacemaker Cell signalling/signal transduction

(Circulation Research. 2000;87:88.)
© 2000 American Heart Association, Inc.

MiniReview

Sustained Inward Current During Pacemaker Depolarization in Mammalian Sinoatrial Node Cells

Tamotsu Mitsuiye, Yasuko Shinagawa, Akinori Noma

From the Department of Physiology, Faculty of Medicine, Kyoto University, Kyoto, Japan.

Correspondence to Akinori Noma, Department of Physiology, Faculty of Medicine, Kyoto University, Sakyo-Ku, Yoshida-Konoe, Kyoto 606-8501, Japan. E-mail noma{at}card.med.kyoto-u.ac.jp

	Abstract

Top Abstract Introduction Dissection of Ist From... Current Density and Kinetics... Single-Channel Recordings Ist During the Slow... References

 
Abstract—Several time- and voltage-dependent ionic currents have been identified in cardiac pacemaker cells, including Na⁺ current, L- and T-type Ca²⁺ currents, hyperpolarization-activated cation current, and various types of delayed rectifier K⁺ currents. Mathematical models have demonstrated that spontaneous action potentials can be reconstructed by incorporating these currents, but relative contributions of individual currents vary widely between different models. In 1995, the presence of a novel inward current that was activated by depolarization to the potential range of the slow diastolic depolarization in rabbit sinoatrial (SA) node cells was reported. Because the current showed little inactivation during depolarizing pulses, it was called the sustained inward current (I_st). A similar current is also found in SA node cells of the guinea pig and rat and in subsidiary pacemaker atrioventricular node cells. Recently, single-channel analysis has revealed a nicardipine-sensitive, 13-pS Na⁺ current, which is activated by depolarization to the diastolic potential range in guinea pig SA node cells. This channel differs from rapid voltage-gated Na⁺ or L-type Ca²⁺ channels both in unitary conductance and gating kinetics. Because I_st was observed only in spontaneously beating SA node cells, ie, it was absent in quiescent cells dissociated from the same SA or atrioventricular node, an important role of I_st for generation of intrinsic cardiac automaticity was suggested. (Circ Res. 2000;87:88-91.)

Key Words: cardiac pacemaker • sinoatrial node • sustained inward current

	Introduction

Top Abstract Introduction Dissection of Ist From... Current Density and Kinetics... Single-Channel Recordings Ist During the Slow... References

 
Voltage- and time-dependent gating mechanisms of ionic channels play a primary role in driving membrane potential changes during the action potential. In cardiac pacemaker sinoatrial (SA) node cells, the rising phase of the action potential is due to activation of the L-type Ca²⁺ channels, and the delayed rectifier K⁺ channels (I_Kr or I_Ks) are activated by this depolarization.^{1 2} After repolarization, I_K slowly deactivates,³ which results in a gradual increase in the permeability ratio of P_Na/P_K of the membrane. In the presence of background inward currents,^{4 5 6 7 8} this induces gradual depolarization of the membrane during diastole (pacemaker depolarization).

In addition to the above basic mechanisms, involvement of voltage-dependent inward currents, such as I_f, is necessary⁹ to explain dynamic changes in the pacemaker depolarization under physiological conditions, such as during the positive chronotropic effect of ß-adrenergic stimulation. Verheijck et al¹⁰ demonstrated that a small I_{Ca, L} can be activated on depolarization to -60 mV from a holding potential of -90 mV, suggesting a role for I_{Ca, L} in the pacemaker modulation, although most studies report that I_{Ca, L} is activated only at potentials less negative than -40 mV.^{11 12} Recently, a novel inward current, I_st, was identified in spontaneously active SA node cells of rabbits,¹³ guinea pigs,¹⁴ and rats¹⁵ and in the atrioventricular (AV) node cells of rabbits.^{16 17} Because I_st is activated by depolarization within the range of slow diastolic depolarization, contribution of I_st to pacemaker depolarization was suggested. In support of this, I_st was identified in spontaneously active cells but was not observed in quiescent cells dissociated from either SA or AV nodes.

The characteristics of I_st in comparison with I_{Ca, L} are summarized in the Table. I_st is increased nearly 2-fold by ß-adrenergic stimulation (isoprenaline 100 nmol/L), and this increase is reversed by adding acetylcholine.¹⁴ I_st is resistant to tetrodotoxin (30 µmol/L) and is blocked by the classical Ca²⁺ antagonists, such as verapamil (1 µmol/L), D600 (0.1 µmol/L), nicardipine (0.25 to 0.5 µmol/L), and heavy metal cations (1 mmol/L Ni²⁺ and Co²⁺).¹³ Interestingly, 40 µmol/L Ni²⁺, which completely blocks I_{Ca, T},¹¹ also blocks I_st by 50%.¹³ I_st is increased by the Ca²⁺ agonist Bay-K8644.¹⁴ These pharmacological characteristics of I_st are similar to those of I_{Ca, L}. However, I_st is distinct from the window component of I_{Ca, L}, various types of Ca²⁺ channels, persistent Na⁺ current in ventricle, the background Na⁺ current, and the Na⁺/Ca²⁺ exchange current. These comparisons were presented elsewhere in the mutual disruption of I_st.¹³

View this table: [in this window] [in a new window]   Table 1. Comparison of Whole-Cell Ist With ICa,L

Although I_st has been described only by our group, similar currents were identified by Denyer and Brown.¹⁸ They used a ramp pulse (0.1 mV · ms^–1 from -70 to +30 mV) and recorded inward current activation on depolarization beyond -60 mV. The current density of 2 pA/pF is comparable with I_st described in rabbit SA node cells. Denyer and Brown¹⁸ attributed the current to a window component of I_{Ca, L}, because it was blocked by 2 µmol/L nifedipine. The ionic selectivity was not examined; this information may have separated I_st from I_{Ca, L}. DiFrancesco⁹ observed a nitrendipine- and Ni²⁺ (100 µmol/L)-sensitive background component, positive to -45 to -50 mV. On hyperpolarization from holding potential of -35 to -45 or -55 mV, the current shifted in the outward direction (negative slope) by 10 to 20 pA. This negative slope in the I-V relation disappeared after administration of nitrendipine. Again, the current was attributed to the I_{Ca, L} window component. However, if the liquid junction potential of the pipette solution¹⁰ is subtracted, the corrected activation threshold of -55 to -60 mV is close to the voltage range for attraction of I_st. However, no current similar to I_st was described in the recent study by Verheijck et al.¹⁰

	Dissection of Ist From the Whole-Cell Current

Top Abstract Introduction Dissection of Ist From... Current Density and Kinetics... Single-Channel Recordings Ist During the Slow... References

 
In whole-cell voltage clamp, separation of I_st from K⁺ conductance was achieved by using a Cs⁺-rich pipette solution. I_f at the holding potential, -80 mV, was blocked by adding 5 mmol/L Cs⁺ to the bath. Unfortunately, unambiguous dissection of I_st was not possible, because no selective blocker is available. However, it was assumed that the inward current induced by depolarization from -80 to -50 mV is attributable to I_st, whereas I_{Ca, L} is activated by more positive depolarization (>-40 mV). In support of this assumption, the sustained inward current at -50 mV was scarcely affected when I_{Ca, L} was suppressed by decreasing [Ca²⁺]_o to 0.1 mmol/L. The disappearance of I_{Ca, L} below 0.1 mmol/L [Ca²⁺]_o is well established by measuring the relationship between [Ca²⁺]_o and I_{Ca, L}.¹¹ Furthermore, the inward current at -50 mV was abolished by removing Na⁺ from the bath solution, whereas I_{Ca, L} remained intact.^{13 14} The complete removal of external Ca²⁺ using EGTA also failed to depress I_st.¹⁴ In this experiment, the Na⁺ conductance through I_{Ca, L} channels^{19 20} was excluded by using 0.5 or 2.3 mmol/L Mg²⁺. Thus, it is concluded that I_st is a current component carried by Na⁺.

The conductance sequence of I_st for monovalent cations was determined to be Na⁺>Li⁺>K⁺=Cs⁺ by totally replacing external Na⁺.²¹ I_st is different from the Na⁺-dependent background current, which is recorded in the presence of Ca²⁺ antagonists and shows a different ion selectivity (K⁺>Cs⁺>Na⁺>Li⁺).²²

	Current Density and Kinetics of Ist

Top Abstract Introduction Dissection of Ist From... Current Density and Kinetics... Single-Channel Recordings Ist During the Slow... References

 
The amplitude of I_st varies between different SA node cells, possibly corresponding to cell-to-cell variation in the rate of spontaneous action potentials. In rabbit myocytes (cellular capacitance, 47±14 pF),¹³ the I_st amplitude was -28.4±2.5 pA at -60 mV and -49.7±4.0 pA at -50 mV. A very similar inward current was observed in AV node cells¹⁶ (34.2±7.8 pF) with a maximum amplitude of 25±20.1 pA at -40 mV. In guinea pig SA node cells (38.6±7.2 pF),¹⁴ I_st was 46.5±10.5 pA at -50 mV. In rat SA node cells,¹⁵ the maximum current density of 2.8 pA/pF was reported.

The relationship between I_st density in primary as opposed to follower pacemaker cells has not been examined, because no clear criteria are available to distinguish the true pacemaker cells from follower cells after dissociating myocytes. Even when cell dissociation is started using a very small tissue segment, dissected from the leading pacemaker site within the SA node, a variety of cell types are found. In the rabbit and guinea pig SA node, most cells with I_st also express I_f.^{13 14}

If I_st has no inactivation gate, I_st will continuously flow at a holding potential of -40 mV and can be deactivated on hyperpolarization. This should result in an outward current jump on hyperpolarization, provided that all currents other than I_st are appropriately blocked. However, no such outward jump is observed. The first study describing I_st¹³ addressed this question and demonstrated very slow inactivation; a 5-second pulse to -10 mV largely inactivated I_st, which recovered with a time constant of 1.36±0.4 seconds at a holding potential of -80 mV. Because this slow inactivation was more apparent when the Ca²⁺ current I_{Ca, L} was intact, Ca²⁺-mediated inactivation was suggested.

	Single-Channel Recordings

Top Abstract Introduction Dissection of Ist From... Current Density and Kinetics... Single-Channel Recordings Ist During the Slow... References

 
A candidate unitary event for whole-cell I_st has been reported by Mitsuiye et al.¹⁷ Using a Na⁺-rich, Ca²⁺-free pipette solution in the cell-attached patch experiments, a novel single-channel current was recorded in addition to the classical Na⁺ and L-type Ca²⁺ channels. The new channel showed no obvious inactivation during 700 ms depolarization, and a smaller amplitude (-1.1±0.18 pA at -60 mV) than Na⁺ (3.3 pA) and L-type Ca²⁺ channels (9.6±0.32 pA at -60 mV in the absence of divalent cations). The average unitary conductance of sustained inward current (SIC) was 13.3 pS and showed a reversal potential at +13 mV. SIC was seen infrequently unless Bay-K8644 was included in the pipette solution. Bath application of nicardipine abolished SIC, and SIC was observed only in spontaneously beating SA node cells. In the ensemble average, the SIC activation occurred over a voltage range encompassing most of the slow diastolic depolarization (>-70 mV). Cumulative histograms for both open and closed times were composed of 2 exponential components. The nicardipine sensitivity, bursting behavior, and voltage-dependent gating of SIC are similar to in cardiac L-type Ca²⁺ channel. However, their latency to the first opening was 2 orders of magnitude longer than in L-type Ca²⁺ channels. Although the kinetic analysis is not completed, the presence of a new channel underlying I_st is suggested by single-channel recordings.

	Ist During the Slow Diastolic Depolarization

Top Abstract Introduction Dissection of Ist From... Current Density and Kinetics... Single-Channel Recordings Ist During the Slow... References

 
To estimate how I_st could contribute to the slow diastolic depolarization, empirical equations were formulated in rats¹⁵ on the basis of 3 assumptions. First, the nicardipine-sensitive sustained inward current recorded at potentials more negative than the activation threshold of I_{Ca, L} (-40 mV) is attributable to I_st. Second, the reversal potential is +18 mV according to both the single channel (+10 to 20 mV) and the whole-cell I_st obtained in the 0.1 mmol/L [Ca²⁺]_o solution. Third, the same formalism as I_{Ca, L} is applicable to I_st.

(1)

where I_st is a whole-cell current (32-pF cell) in pA, d and f are the activation and inactivation gate parameters, respectively, and E is the membrane potential (mV). The voltage dependence of rate constants _d, ß_d, _f, and ß_f (sec^-1) was adjusted to simulate the experimental record.

(2)

(3)

(4)

(5)

The thick traces in the Figure are I_st during the voltage clamp, adjusted to the experimental records from -70 to -40 mV. The thin curves that denote I_{Ca, L} are calculated by modifying the equations described in mathematical models^{4 5 6 7 8} to account for the experimental whole-cell current being the sum of I_st and I_{Ca, L} (dotted curves). Although the quantitative detail of I_{Ca, L} is not critically examined, the Figure is useful in describing our hypothesis; namely, the whole-cell current is due largely to I_st at potentials more negative than -50 mV. At less negative potentials, the noninactivated component of I_{Ca, L} overlaps I_st.

View larger version (49K): [in this window] [in a new window]   Figure 1. Schematic illustration of Ist and ICa, L during the voltage clamp (A) and Ist during spontaneous action potentials (B), which were recorded from a single rat SA node cell. A, Voltage pulse started at 50 ms and lasted for 600 ms. The current amplitudes of both Ist and ICa, L were adjusted to be representative of a hypothetical cell of 32 pF from the rat SA node. B, Action potentials were recorded with the amphotericin-perforated patch method. The lower graph illustrates Ist, which was calculated using Equations 1 through 5. (Adapted from Shinagawa Y, Satoh H, Noma A. The sustained inward current and inward rectifier K+ current in pacemaker cells dissociated from rat sinoatrial node. J Physiol [Lond]. 2000;523:593–605.)

Panel B of the Figure illustrates the time course and magnitude of I_st during spontaneous action potentials, sampled at 2 kHz. Gating parameters of I_st were calculated bit by bit during each sampling interval at the voltage of individual sample points using the above equations. The amplitude of I_st approaches zero at the overshoot, which is nearly equal to the reversal potential of I_st. During the early phase of repolarization, the driving force for I_st becomes larger, and finally near the maximum diastolic potential the channel is largely deactivated. During diastole, the gradual increase in amplitude is due to the time-dependent increase in the activation parameter d. The action potential clamp experiment in SA node cells revealed a D600-sensitive inward current component of -10 to -20 pA during the diastolic period.²³ The authors attributed this current to I_{Ca, L}, but part of this component might be due to I_st.

The activation of I_st and gradual depolarization constitute a positive feedback loop during diastole to drive slow diastolic depolarization. The same mechanism is suggested for I_{Ca, L} in rabbits.¹⁰ The contribution of tetrodotoxin-sensitive Na⁺ current to spontaneous activity in newborn rabbit SA node cells is also due to a positive feedback.²⁴ These effects are in contrast to the self-limiting process of voltage-dependent deactivation of I_K during diastole. I_f is activated by hyperpolarization but not by depolarization.

The successful reconstruction of SA node action potentials by various types of computer models,^{4 5 6 7 8} without including I_st, indicates that the spontaneous activity can be generated by an appropriate but variable combination of time- and voltage-dependent currents. Furthermore, the amplitudes or kinetics of individual currents are not necessarily identical in different types of models. However, the kinetic characteristic for a given current system should confer a unique and important role to that current system in generating the pacemaker activity. Because the voltage-dependent kinetics are totally different among I_{Ca, L}, I_st, I_f, and I_Kr, they may take qualitatively different roles. To clarify the role specific to I_st, it is necessary to construct a mathematical model that includes I_st.

	Acknowledgments

 
This work was supported by a research grant from the Ministry of Education, Science, and Culture of Japan. We wish to thank Dr T. Powell for reading the manuscript and for useful suggestions.

Received February 2, 2000; accepted May 26, 2000.

	References

Top Abstract Introduction Dissection of Ist From... Current Density and Kinetics... Single-Channel Recordings Ist During the Slow... References

 
1. Irisawa H, Brown HF, Giles W. Cardiac pacemaking in the sinoatrial node. Physiol Rev. 1993;73:197–227.[Free Full Text]

2. Campbell DL, Rasmusson RL, Strauss HC. Ionic current mechanisms generating vertebrate primary cardiac pacemaker activity at the single cell level: an integrative view. Annu Rev Physiol. 1992;54:279–302.[Medline] [Order article via Infotrieve]

3. Ono K, Ito H. Role of rapidly activating delayed rectifier K⁺ current in sinoatrial node pacemaker activity. Am J Physiol. 1995;269:H453–H462.[Abstract/Free Full Text]

4. Yanagihara K, Noma A, Irisawa H. Reconstruction of sino-atrial node pacemaker potential based on the voltage clamp experiments. Jpn J Physiol. 1980;30:841–857.[Medline] [Order article via Infotrieve]

5. Noble D, Noble SJ. A model of sino-atrial node electrical activity based on a modification of the DiFrancesco-Noble (1984) equations. Proc R Soc Lond B Biol Sci. 1984;222:295–304.[Medline] [Order article via Infotrieve]

6. Rasmusson RL, Clark JW, Giles WR, Shibata EF, Campbell DL. A mathematical model of a bullfrog cardiac pacemaker cell. Am J Physiol. 1990;259:H352–H369.[Abstract/Free Full Text]

7. Wilders R, Jongsma HJ, van Ginneken AC. Pacemaker activity of the rabbit sinoatrial node: a comparison of mathematical models. Biophys J. 1991;60:1202–1216.[Medline] [Order article via Infotrieve]

8. Demir SS, Clark JW, Murphey CR, Giles WR. A mathematical model of a rabbit sinoatrial node cell. Am J Physiol. 1994;266:C832–C852.[Abstract/Free Full Text]

9. DiFrancesco D. The contribution of the "pacemaker" current (i_f) to generation of spontaneous activity in rabbit sino-atrial node myocytes. J Physiol (Lond). 1991;434:23–40.[Abstract/Free Full Text]

10. Verheijck EE, van Ginneken ACG, Wilders R, Bouman LN. Contribution of L-type Ca²⁺ current to electrical activity in sinoatrial nodal myocytes of rabbits. Am J Physiol. 1999;276:H1064–H1077.[Abstract/Free Full Text]

11. Hagiwara N, Irisawa H, Kameyama M. Contribution of two types of calcium currents to the pacemaker potentials of rabbit sino-atrial node cells. J Physiol (Lond). 1988;395:233–253.[Abstract/Free Full Text]

12. McDonald TF, Pelzer S, Trautwein W, Pelzer DJ. Regulation and modulation of calcium channels in cardiac, skeletal, and smooth muscle cells. Physiol Rev. 1994;74:365–507.[Free Full Text]

13. Guo J, Ono K, Noma A. A sustained inward current activated at the diastolic potential range in rabbit sino-atrial node cells. J Physiol (Lond).. 1995;483:1–13.[Abstract/Free Full Text]

14. Guo J, Mitsuiye T, Noma A. The sustained inward current in sino-atrial node cells of guinea-pig heart. Pflügers Arch. 1997;433:390–396.

15. Shinagawa Y, Satoh H, Noma A. The sustained inward current and inward rectifier K⁺ current in pacemaker cells dissociated from rat sinoatrial node. J Physiol (Lond).. 2000;523:593–605.[Abstract/Free Full Text]

16. Guo J, Noma A. Existence of a low-threshold and sustained inward current in rabbit atrio-ventricular node cells. Jpn J Physiol. 1997;47:355–359.[Medline] [Order article via Infotrieve]

17. Mitsuiye T, Guo J, Noma A. Nicardipine-sensitive Na⁺ channels in sinoatrial node cells of guinea-pig heart. J Physiol (Lond). 1999;521:69–79.[Abstract/Free Full Text]

18. Denyer JC, Brown HF. Calcium "window" current in rabbit isolated sino-atrial node cells. J Physiol (Lond). 1990;429:21P. Abstract.

19. Hess P, Lansman JB, Tsien RW. Calcium channel selectivity for divalent and monovalent cations: voltage and concentration dependence of single channel current in ventricular heart cells. J Gen Physiol. 1986;88:293–319.[Abstract/Free Full Text]

20. Matsuda H. Sodium conductance in calcium channels of guinea-pig ventricular cells induced by removal of external calcium ions. Pflügers Arch. 1986;407:465–475.

21. Guo J, Ono K, Noma A. Monovalent cation conductance of the sustained inward current in rabbit sinoatrial node cells. Pflügers Arch. 1996;433:209–211.

22. Hagiwara N, Irisawa H, Kasanuki H, Hosoda S. Background current in sino-atrial node cells of the rabbit heart. J Physiol (Lond). 1992;448:53–72.[Abstract/Free Full Text]

23. Doerr TH, Denger R, Trautwein W. Calcium currents in single SA nodal cells of the rabbit heart studied with action potential clamp. Pflügers Arch. 1989;413:599–603.

24. Baruscotti M, DiFrancesco D, Robinson RB. A TTX-sensitive inward sodium current contributes to spontaneous activity in newborn rabbit sino-atrial node cells. J Physiol (Lond). 1996;492:21–30.[Abstract/Free Full Text]

This article has been cited by other articles:

				M. E. Mangoni and J. Nargeot Genesis and Regulation of the Heart Automaticity Physiol Rev, July 1, 2008; 88(3): 919 - 982. [Abstract] [Full Text] [PDF]

				J. Liu, H. Dobrzynski, J. Yanni, M. R. Boyett, and M. Lei Organisation of the mouse sinoatrial node: structure and expression of HCN channels Cardiovasc Res, March 1, 2007; 73(4): 729 - 738. [Abstract] [Full Text] [PDF]

				D. M. Bers The Beat Goes On: Diastolic Noise That Just Won't Quit Circ. Res., October 27, 2006; 99(9): 921 - 923. [Full Text] [PDF]

				J. Stieber, K. Wieland, G. Stockl, A. Ludwig, and F. Hofmann Bradycardic and Proarrhythmic Properties of Sinus Node Inhibitors Mol. Pharmacol., April 1, 2006; 69(4): 1328 - 1337. [Abstract] [Full Text] [PDF]

				M. S. Wolin and S. A. Gupte Novel Roles for Nox Oxidases in Cardiac Arrhythmia and Oxidized Glutathione Export in Endothelial Function Circ. Res., September 30, 2005; 97(7): 612 - 614. [Full Text] [PDF]

				M. Lei, C. Goddard, J. Liu, A.-L. Leoni, A. Royer, S. S.-M. Fung, G. Xiao, A. Ma, H. Zhang, F. Charpentier, et al. Sinus node dysfunction following targeted disruption of the murine cardiac sodium channel gene Scn5a J. Physiol., September 1, 2005; 567(2): 387 - 400. [Abstract] [Full Text] [PDF]

				T. Krogh-Madsen, P. Schaffer, A. D. Skriver, L. K. Taylor, B. Pelzmann, B. Koidl, and M. R. Guevara An ionic model for rhythmic activity in small clusters of embryonic chick ventricular cells Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H398 - H413. [Abstract] [Full Text] [PDF]

				D. J. Huelsing, K. W. Spitzer, and A. E. Pollard Spontaneous activity induced in rabbit Purkinje myocytes during coupling to a depolarized model cell Cardiovasc Res, September 1, 2003; 59(3): 620 - 627. [Abstract] [Full Text] [PDF]

				Y. Kito and H. Suzuki Pacemaker frequency is increased by sodium nitroprusside in the guinea pig gastric antrum J. Physiol., January 1, 2003; 546(1): 191 - 205. [Abstract] [Full Text] [PDF]

				Y. Kurata, I. Hisatome, S. Imanishi, and T. Shibamoto Dynamical description of sinoatrial node pacemaking: improved mathematical model for primary pacemaker cell Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H2074 - H2101. [Abstract] [Full Text] [PDF]

				G. Schram, M. Pourrier, P. Melnyk, and S. Nattel Differential Distribution of Cardiac Ion Channel Expression as a Basis for Regional Specialization in Electrical Function Circ. Res., May 17, 2002; 90(9): 939 - 950. [Abstract] [Full Text] [PDF]

				D. M. Bers Calcium and Cardiac Rhythms: Physiological and Pathophysiological Circ. Res., January 11, 2002; 90(1): 14 - 17. [Full Text] [PDF]

				M. E. Mangoni and J. Nargeot Properties of the hyperpolarization-activated current (If) in isolated mouse sino-atrial cells Cardiovasc Res, October 1, 2001; 52(1): 51 - 64. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mitsuiye, T. Articles by Noma, A. Search for Related Content PubMed PubMed Citation Articles by Mitsuiye, T. Articles by Noma, A. Related Collections Electrophysiology Pacemaker Cell signalling/signal transduction