Recent electrophysiological data have provided the evidences that background currents such as Na(+)-Ca2+ exchange can significantly modulate cardiac pacemaker activity. In this study, the effects of extracellular Na+ and Ca2+ concentrations on the pacemaker activity were investigated by measuring the intracellular Na+ activity (aiNa) with Na(+)-selective microelectrodes and the results are summarized as follows. 1) In the rabbit SA node, aiNa was 3.2 +/- 0.3 mM and mean MDP (maximal diastolic potential) was -63.3 +/- 1.4 mV. 2) Graded decreases of external Na+ concentration resulted in the loss of spontaneous beating, hyperpolarization and the decrease of aiNa. 3) An increase in extracellular Ca2+ concentration in low Na+ solution augmented the transient decrease of aiNa, about 3 minutes in low Na+ solution, until aiNa started to increase. 4) In low Na+ solution, which had extracellular Ca2+ concentration according to the calculation based on the equilibrium state of Na+-Ca2+ exchange, aiNa was continuously decreased. It was concluded that intracellular Na+ activity modulated by Na+-Ca2+ exchange could play an important role in the initiation of pacemaker potential.
Action Potentials ; Animal ; Biological Transport ; Calcium/*metabolism/physiology ; Electrophysiology ; Female ; Male ; Pacemaker, Artificial ; Rabbits ; Sinoatrial Node/*metabolism/physiology ; Sodium/*metabolism/physiology ; Support, Non-U.S. Gov't

AIMTo investigate the effects of exogenous NO donors sodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1) on automaticity of the rabbit sino-atrial node in vitro and the action mechanism.

METHODSThe intracellular microelectrode technique is used to record the action potentials of rabbit sino-atrial node and APA (amplitude of AP), V(max) (maximal rate of depolarization), VDD (velocity of diastolic depolarization), RPF (rate of pacemaker firing) are analyzed.

RESULTSSNP(10(-5) - 10(-2) mol/L) increased its RPF and VDD dose-dependently. 10(-3) mol/L SNP increased RPF (beats/min) from 163 +/- 10.8 to 195.0 +/- 13.1 increased VDD (mV/s) from 50.3 +/- 9.6 to 70.2 +/- 12.1 (P < 0.01). SIN-1(10(-3) - 10(-2) mol/L) also increased RPF and VDD (P < 0.01).10(-4) mo/L Methylene blue (MB), a blocker of GMP cyclase, prevented the positive chronotropic effect and increasement of VDD induced by 10(-3) mol/L SNP totally (P < 0.01). 2. CsCl (2 mmol/L), a blocker of I(f) prevented the increasement of RPF and VDD in part (P < 0.05). 3. NIF (0.46 micromol/L), a blocker of I(Ca-L, had no significant effects on chronotropic effect and increasement of VDD (P < 0.01).

CONCLUSIONExogenous NO can increase the automaticity of rabbit sino-atrial node in vitro. The chronotropic effect is involved in NO-cGMP pathway and results from increasement of I(f) in the sino-atrial node at least in part; I(ca-L) is unlikely to play a major role in this effect.

Action Potentials ; Animals ; Heart Rate ; Molsidomine ; analogs & derivatives ; pharmacology ; Nitric Oxide ; metabolism ; Nitroprusside ; pharmacology ; Rabbits ; Sinoatrial Node ; drug effects ; physiology

OBJECTIVE: To study the distribution and proportion of neuropeptide containing nervers in the sinus node in cases of sudden manhood death syndrome (SMDS) and to explore the mechanism of SMDS. METHODS: Immunohistochemical staining and quantitative analysis of neuropeptide Y (NPY) and vasoactive intestinal peptide(VIP) in the sinus node in 6 cases of SMDS and in 12 cases of non-cardiac death(control group) were achieved by LSAB method and computerized image system. RESULTS: As for NPY positive materials, VIP positive materials and the ratio of VIP/NPY in the sinus nodes, there were no significant difference between the control group and SMDS group. CONCLUSION The mechanism of SMDS and the abnormality of autonomic nervous innervation in the sinoatrial nodes maybe incorrelation.
Adult ; Autonomic Nervous System/physiology* ; Death, Sudden/pathology* ; Humans ; Immunohistochemistry ; Male ; Myocardium/metabolism* ; Neuropeptide Y/metabolism* ; Sinoatrial Node/innervation* ; Vasoactive Intestinal Peptide/metabolism*

The study was aimed to assess the effect of Klotho gene and sinoatrial node pacing channel gene (HCN4 and HCN2) for studying sick sinus syndrome, with Klotho gene under the interference of Plasmid-mediated short hairpin RNA. Twenty-five C57BL/6J mice were divided into four groups, i. e, plasmid shRNA 24h group, plasmid shRNA 12h group, sodium chloride 24h group and sodium chloride 12h group. Plasmid shRNA 50microL (1microg/microL) and sodium chloride 50microl were respectively injected according to mice vena caudalis into those in plasmid shRNA group and sodium chloride group. After 12h or 24h respectively, all mice were executed and their sinoatrial node tissues were cut. The mRNA of Klotho, HCN4 and HCN2 gene were detected by RT-PCR. The results of RT-PCR showed that Klotho, HCN4 and HCN2 mRNA levels were lower compared with those in sodium chloride 12h group after 12h interference interval. The results indicated that there might be the a certain relationship between Klotho gene and sinoatrial node pacing channel gene.
Animals ; Glucuronidase ; genetics ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Plasmids ; genetics ; Potassium Channels ; genetics ; metabolism ; RNA Interference ; RNA, Messenger ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; Sinoatrial Node ; metabolism ; physiology ; physiopathology

OBJECTIVETo detect the expression of voltage-gated Na(+) channel (NaCh) isoforms in rat sinoatrial node and explore their functions.

METHODSExpressions of NaCh isoforms Nav1.1, Nav1.2, Nav1.3, Nav1.5, Nav1.6 and Nav1.7 in the rat sinoatrial node were detected by immunohistochemistry. The functional roles of the NaChs were tested by observing the effect of tetrodotoxin, a specific blocker of NaChs, on the intrinsic heart rate of isolated rat working heart.

RESULTSThe tetrodotoxin- sensitive neuronal isoforms Nav1.1, Nav1.6 and Nav1.7 as well as the tetrodotoxin-resistant cardiac isoform Nav1.5 were present in the rat sinoatrial node, and the neuronal isoforms were more abundant than Nav1.5 (P<0.05). The selective blockade of tetrodotoxin-sensitive isoforms (presumably Nav1.1, Nav1.6 and Nav1.7) by 100 nmol/L tetrodotoxin scarcely affected the intrinsic heart rate (0.5-/+2.9%, P>0.05) while blockade of tetrodotoxin-resistant isoform (presumably Nav1.5) by 2 micromol/L tetrodotoxin resulted in an obvious decline in the intrinsic heart rate (22.1-/+2.1%, P<0.001).

CONCLUSIONSNav1.1, Nav1.5, Nav1.6 and Nav1.7 are all present in rat sinoatrial node. Although neuronal isoforms are more abundant, Nav1.5 seems to contribute more to activity of the sinoatrial node.

Animals ; Heart Rate ; drug effects ; physiology ; Immunohistochemistry ; Ion Channel Gating ; drug effects ; physiology ; Male ; NAV1.1 Voltage-Gated Sodium Channel ; NAV1.5 Voltage-Gated Sodium Channel ; NAV1.6 Voltage-Gated Sodium Channel ; Nerve Tissue Proteins ; biosynthesis ; Protein Isoforms ; biosynthesis ; Rats ; Sinoatrial Node ; drug effects ; metabolism ; physiology ; Sodium Channels ; biosynthesis ; Tetrodotoxin ; pharmacology