The sinus node is prone to disease in particular sick sinus syndrome which leads to a 
pathologically slow heart rate and can be accompanied by sinus arrest leading to dizziness and loss of consciousness [ 111 , 112 ]. The disease increases in incidence with age and has been attributed to progressive cell loss and fibrosis [ 111 , 112 ]. However it also clear that there are changes in the expression of relevant pacemaking genes in the SA node with age. For example HCN4 and SERCA2 decrease in expression and this may be responsible for the decline in intrinsic heart rate with age [ 14 , 113 – 116 ]. It may also be contributing to physiological and pathological adaptations too [ 117 , 118 ]. The SAN is supplied by SAN artery which usually arises from the right coronary artery in man though there are anatomical variations. The SA node responds to hypoxia and ischaemia with heart rate slowing and ultimately failure due to exit block from the SA node into the atrium [ 119 ]. In modelling work, a major component of the response to hypoxia is the opening of KATP channels [ 119 ]. Potential shortening of the action potential duration is offset by increases in calcium current but the membrane potential becomes hyperpolarised and the pacemaker depolarization is slowed. Interestingly, these effects are exacerbated by concomitant increased vagal activity [ 119 ].
We investigated this issue in a different way [ 98 ]. Using an ex-vivo Langendorff preparation we measured spontaneous firing using a multielectrode array. We measured the sinus node recovery time by overdrive pacing the endogenous activity and then stopping the pacing and measured the time it takes for the SAN to recover spontaneous activity. This measure is used clinically to assess SAN function and in hypoxic conditions in control mice we found it became prolonged [ 98 ]. This may be a protective response where a reduction in activity helps preserve the viability of SAN myocytes. In contrast in the cKO mice the SAN recovery time did not prolong with hypoxia and under resting conditions was longer. This lack of flexibility age. The contribution of KATP to SAN physiology and pathophysiology is summarized in Figure 3 .
It leads to bradycardia and ultimately SAN inability
Ideal remembered getting currently talking about brand new 1967 Frank and you will Nancy Sinatra graph-topper “Somethin’ Dumb,” songwriter C. Carson Areas was born in Philadelphia towards e Clarence from the beginning, he was the brand new eldest out of four youngsters, good brood one provided more youthful sibling Van Dyke. When you’re gonna brand new University out of Miami, Parks befriended other scholar Bernie Armstrong, and you may shortly after graduation each other got from inside the Ca, where they based the latest Steeltown A couple, a people duo regarding shape of your own Kingston Threesome. Within the 1959 the fresh new Steeltown Two filed its first unmarried, “The newest Wolves,” toward smaller Gini name. Immediately after giving a follow-right up, “The newest Potter’s Controls,” with the just as small Neophon imprint, Areas and you will Armstrong acknowledged an offer from Terry Gilkyson and you can Rich Dehr to join their reconstituted Effortless Bikers, recording a set of LPs getting Decca — . See Complete Bio
Musician Bio
Most readily useful remembered getting authoring the newest 1967 Honest and you will Nancy Sinatra graph-topper “Somethin’ Stupid,” songwriter C. Carson Areas grew up in Philadelphia for the age Clarence on delivery, he was this new earliest out-of four students, a great brood you to definitely integrated younger brother Van Dyke. While browsing the fresh new School out of Miami, Parks befriended fellow scholar Bernie Armstrong, and once graduation both arrived in Ca, in which they based the fresh Steeltown A couple of, a visitors duo about shape of your own Kingston Trio. In the 1959 the brand new Steeltown A couple registered its first single, “The newest Wolves,” on tiny Gini name.