Effects of articaine on action potential characteristics and the underlying ion currents in canine ventricular myocytes

Due to the limited availability of healthy human ventricular tissues, the most suitable animal model has to be applied for electrophysiological and pharmacological studies. This can be best identified by studying the properties of ion currents shaping the action potential in the frequently used laboratory animals, such as dogs, rabbits, guinea pigs, or rats, and comparing them to those of human cardiomyocytes. The authors of this article with the experience of three decades of electrophysiological studies, performed in mammalian and human ventricular tissues and isolated cardiomyocytes, summarize their results obtained regarding the major canine and human cardiac ion currents. Accordingly, L-type Ca2+ current (ICa), late Na+ current (INa-late), rapid and slow components of the delayed rectifier K+ current (IKr and IKs, respectively), inward rectifier K+ current (IK1), transient outward K+ current (Ito1), and Na+/Ca2+ exchange current (INCX) were characterized and compared. Importantly, many of these measurements were performed using the action potential voltage clamp technique allowing for visualization of the actual current profiles flowing during the ventricular action potential. Densities and shapes of these ion currents, as well as the action potential configuration, were similar in human and canine ventricular cells, except for the density of IK1 and the recovery kinetics of Ito. IK1 displayed a largely four-fold larger density in canine than human myocytes, and Ito recovery from inactivation displayed a somewhat different time course in the two species. On the basis of these results, it is concluded that canine ventricular cells represent a reasonably good model for human myocytes for electrophysiological studies, however, it must be borne in mind that due to their stronger IK1, the repolarization reserve is more pronounced in canine cells, and moderate differences in the frequency-dependent repolarization patterns can also be anticipated.

Download Full-text

Dynamics of the inward rectifier K+ current during the action potential of guinea pig ventricular myocytes

Biophysical Journal ◽

10.1016/s0006-3495(91)82187-7 ◽

1991 ◽

Vol 60 (6) ◽

pp. 1534-1539 ◽

Cited By ~ 39

Author(s):

J. Ibarra ◽

G.E. Morley ◽

M. Delmar

Keyword(s):

Guinea Pig ◽

Action Potential ◽

Ventricular Myocytes ◽

Inward Rectifier ◽

K Current

Download Full-text

Effects of estrogen on action potential and membrane currents in guinea pig ventricular myocytes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.277.2.h826 ◽

1999 ◽

Vol 277 (2) ◽

pp. H826-H833 ◽

Cited By ~ 12

Author(s):

Seiko Tanabe ◽

Toshio Hata ◽

Masayasu Hiraoka

Keyword(s):

Guinea Pig ◽

Action Potential ◽

Action Potentials ◽

Voltage Dependence ◽

Ventricular Myocytes ◽

Membrane Currents ◽

Patch Clamp Technique ◽

17Β Estradiol ◽

Electrophysiological Effects ◽

Ionic Basis

To explore a possible ionic basis for the prolonged Q-T interval in women compared with that in men, we investigated the electrophysiological effects of estrogen in isolated guinea pig ventricular myocytes. Action potentials and membrane currents were recorded using the whole cell configuration of the patch-clamp technique. Application of 17β-estradiol (10–30 μM) significantly prolonged the action potential duration (APD) at 20% (APD20) and 90% repolarization (APD90) at stimulation rates of 0.1–2.0 Hz. In the presence of 30 μM 17β-estradiol, APD20 and APD90 at 0.1 Hz were prolonged by 46.2 ± 17.1 and 63.4 ± 11.7% of the control ( n = 5), respectively. In the presence of 30 μM 17β-estradiol the peak inward Ca2+ current ( I CaL) was decreased to 80.1 ± 2.5% of the control ( n = 4) without a shift in its voltage dependence. Application of 30 μM 17β-estradiol decreased the rapidly activating component of the delayed outward K+ current ( I Kr) to 63.4 ± 8% and the slowly activating component ( I Ks) to 65.8 ± 8.7% with respect to the control; the inward rectifier K+ current was barely affected. The results suggest that 17β-estradiol prolonged APD mainly by inhibiting the I Kcomponents I Krand I Ks.

Download Full-text

Dual effects of external magnesium on action potential duration in guinea pig ventricular myocytes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.268.6.h2321 ◽

1995 ◽

Vol 268 (6) ◽

pp. H2321-H2328 ◽

Cited By ~ 3

Author(s):

S. Zhang ◽

T. Sawanobori ◽

H. Adaniya ◽

Y. Hirano ◽

M. Hiraoka

Keyword(s):

Guinea Pig ◽

Action Potential ◽

Decay Time ◽

Action Potential Duration ◽

Time Course ◽

Ventricular Myocytes ◽

Membrane Surface ◽

Surface Charges ◽

Whole Cell Patch Clamp ◽

K Current

Effects of extracellular magnesium (Mg2+) on action potential duration (APD) and underlying membrane currents in guinea pig ventricular myocytes were studied by using the whole cell patch-clamp method. Increasing external Mg2+ concentration [Mg2+]o) from 0.5 to 3 mM produced a prolongation of APD at 90% repolarization (APD90), whereas 5 and 10 mM Mg2+ shortened it. [Mg2+]o, at 3 mM or higher, suppressed the delayed outward K+ current and the inward rectifier K+ current. Increases in [Mg2+]o depressed the peak amplitude and delayed the decay time course of the Ca2+ current (ICa), the latter effect is probably due to the decrease in Ca(2+)-induced inactivation. Thus 3 mM Mg2+ suppressed the peak ICa but increased the late ICa amplitude at the end of a 200-ms depolarization pulse, whereas 10 mM Mg2+ suppressed both components. Application of 10 mM Mg2+ shifted the voltage-dependent activation and inactivation by approximately 10 mV to more positive voltage due to screening the membrane surface charges. Application of manganese (1-5 mM) also caused dual effects on APD90, similar to those of Mg2+, and suppressed the peak ICa with slowed decay. These results suggest that the dual effects of Mg2+ on APD in guinea pig ventricular myocytes can be, at least in part, explained by its action on ICa with slowed decay time course in addition to suppressive effects on K+ currents.

Download Full-text

Characterization of a TTX-sensitive Na+ current in pacemaker cells isolated from rabbit sinoatrial node

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.270.6.h2108 ◽

1996 ◽

Vol 270 (6) ◽

pp. H2108-H2119 ◽

Cited By ~ 15

Author(s):

H. Muramatsu ◽

A. R. Zou ◽

G. A. Berkowitz ◽

R. D. Nathan

Keyword(s):

Action Potential ◽

Ventricular Myocytes ◽

Pacemaker Cells ◽

Na Current ◽

Recovery From Inactivation ◽

Cell Recording ◽

Rabbit Sinoatrial Node ◽

Best Fit ◽

Maximum Conductance

A tetrodotoxin (TTX)-sensitive Na+ current (iNa) was investigated in single pacemaker cells after 1-4 days in culture. Ruptured-patch and perforated-patch whole cell recording techniques were used to record iNa and spontaneous electrical activity, respectively. For seven cells exposed to 20 mM Na+ (22-24 degrees C) and held at -98 mV (25% of the channels inactivated), the uncorrected maximum iNa was -39 +/- 10 pA/pF at -29.1 +/- 2.4 (SE) mV, maximum conductance was 0.9 +/- 0.2 nS/pF (1.6 +/- 0.2 mS/cm2). Half-activation and inactivation potentials were -41.4 +/- 2.0 and -90.6 +/- 2.5 mV, and the corresponding slope factors were 6.0 +/- 0.4 and 6.4 +/- 0.6 mV. Inactivation and recovery from inactivation were best fit by sums of two exponentials. During action potential clamp, a TTX-sensitive compensation current accounted for 55% of the upstroke velocity. The results suggest that iNa contributes significantly to the action potential in some nodal pacemaker cells, and the characteristics of iNa are similar to those of atrial and ventricular myocytes.

Download Full-text