Membrane currents in the rabbit sinoatrial node cell studied by the double microelectrode method
A. Noma, H. Irisawa

This paper constitutes a landmark in the study of mechanisms underlying generation of sinoatrial nodal (SAN) activity...

How does adrenaline accelerate the heart?
H. F. Brown, D. DiFrancesco, S. J. Noble

Modulation of the activity of the sinoatrial node (SAN) underpins the autonomic regulation of heart rate, and this paper provides a wonderful early insight into the mechanism(s) by which adrenaline modulates SAN activity...

Functional and morphological organization of the rabbit sinus node
W. K. Bleeker, A. J. Mackaay, M. Masson-Pevet, L. N. Bouman, A. E. Becker

In order to gain an integrated understanding of the generation and conduction of sinoatrial node (SAN) activity, two types of experimental data are required: first, those data that provide insight into the ionic basis of impulse generation at the cellular level and, second, those indicating how impulse propagation occurs through the intact node and between this and adjacent atrial tissue...

Acetylcholine activation of single muscarinic K+ channels in isolated pacemaker cells of the mammalian heart
B. Sakmann, A. Noma, W. Trautwein

Prior to this study, the ability of acetylcholine (ACh) to increase potassium conductance of pacemaker tissue had already been recognized...

Retarding effect of lowered heart rate on coronary atherosclerosis
P. A. Beere, S. Glagov, C. K. Zarins

Why doesn’t atherosclerosis affect all human arteries equally? This is an important question as areas around arterial branch points and curves are particularly susceptible, and the coronary arteries, the abdominal aortic segment, carotid bifurcation, and vessels supplying lower extremities tend to be affected in a much worse way by atherosclerosis than do other major arteries...

Mechanism of beneficial effect of beta-adrenergic blockade on exercise-induced myocardial ischemia in conscious dogs
B. D. Guth, G. Heusch, R. Seitelberger, J. Ross Jr

Guth et al performed this study against a background in which, while a number of drugs were known to be beneficial in treating effortinduced angina pectoris, precise mechanisms underlying the beneficial effects had not been established...

Muscarinic modulation of cardiac rate at low acetylcholine concentrations
D. DiFrancesco, P. Ducouret, R. B. Robinson

By the time this study was conducted, it was known that acetylcholine (ACh) could modulate multiple ionic currents: activation of a K+ conductance (IKACh, see summary of paper by Sakmann et al, page 53 ), reduction of the slow inward current (Isi), and inhibition of If had all been reported...

Molecular characterization of the hyperpolarization-activated cation channel in rabbit heart sinoatrial node
T. M. Ishii, M. Takano, L. H. Xie, A. Noma, H. Ohmori

Although, historically, the patch-clamp technique was pivotal in establishing the ion channel concept, few would argue against the view that the development of molecular cloning techniques was the next technical advance to revolutionize the study of ion channel function...

The hyperpolarization-activated channel HCN4 is required for the generation of pacemaker action potentials in the embryonic heart
J. Stieber, S. Herrmann, S. Feil, J. Loster, R. Feil, M. Biel, F. Hofmann, A. Ludwig

It is one thing to demonstrate the presence of an ion channel candidate in a particular tissue type, but it is quite another to elucidate its contribution to that tissue’s functional activity...

Long-term prognostic value of resting heart rate in patients with suspected or proven coronary artery disease
A. Diaz, M. G. Bourassa, M. C. Guertin, J. C. Tardif

Perhaps it is fitting to save the most recent study selected for comment until last. A number of epidemiological studies in the literature now point toward the significance of a high resting heart rate in humans, with recognized associations between resting heart rate and mortality in patients with hypertension, metabolic syndrome, and in elderly subjects...