Biomedical Engineering Reference
In-Depth Information
capacity to selectively reduce heart rate act by specifically inhibiting f-channel
function. Related compounds that could potentially be used for the treatment of
diseases such as angina and heart failure are also discussed.
Keywords Brain HCN Heart
I
f
I
h
Ivabradine Pacemaker
Abbreviations
CAD
Coronary artery disease
cAMP
Cyclic adenosine monophosphate
cGMP
Cyclic ganosine monophosphate
CNBD
Cyclic nucleotide binding domain
HCN
Hyperpolarization-activated cyclic nucleotide-gated
I
h
HEK293
Human Embryonic Kidney 293 cells
I
f
Funny current
I
h
Hyperpolarization-activated current
Kv
Voltage-gated potassium channel
LTP
Long-term synaptic plasticity
MI
Myocardial Infarction
PKA
Protein Kinase A
PKC
Protein Kinase C
pS
Pico-Siemens
SAN
Sinoatrial node
1
Introduction
Noma and Irisawa [
1
] first reported the existence in sinoatrial node (SAN) tissue of
a slow, time-dependent inward current that was activated by membrane hyperpo-
larization. This current has perplexed physiologists since it was first discovered.
Initially, its properties were deemed exclusive, for which it has invariably been
named
I
h
(h for hyperpolarization-activated),
I
f
(f for funny), or
I
q
(q for queer).
Similar currents were later revealed in a diverse range of neuronal and nonneuronal
cells, and today these currents are recognized as ubiquitous components of the
nervous system. The current contributes to normal pacemaking activity in the
sinoatrial and atrioventricular nodes in the atria, and Purkinje fibers in the ventricle
[
2
,
3
]. It also plays a role in abnormal spontaneous activity of cardiac myocytes
under pathological conditions [
4
]. The pacemaker current also mediates repetitive
firing in neurons and oscillatory activities in neuronal networks. In addition, this
current acts to set the resting membrane potential of certain excitatory cells, and
