BIO254:Pacemaker
Due Date: 11/20
Description
A pacemaker is an endogenous biological rhythm generator. Pacemakers are also known as biological oscillators, clocks, or timers. Pacemakers control the timing of many biological processes and functions including heart rate, cell division in embryogenesis, and circadian activity level. Pacemakers are found in most organisms including fungi, plants, insects, and mammals. A defining feature of a pacemaker is that it will continue to oscillate even in the absence of external cues. This is in contrast to external regulators of activity such as thermoregulation of lizard activity level by the warming of the sun. In general the role of pacemakers is to allow an organism to anticipate and react to cyclic phenomena. The study of pacemakers is a subset of chronobiology, the study of biological rhythms.
Entrainment
Despite being self-contained, many pacemakers can be entrained (synchronized) by input from external cues such as light. These cues are often linked to physical phenomena such as the rotation of the Earth about its own axis, the orbit of the Earth around the sun, and the tides directed by the orbit of the Moon around the Earth. Pacemakers that are linked to external phenomena are called circa and the rest are called non-circa (Hosn, 1997). Non-circa pacemakers are not synchronized to external cycles but may still be influenced by external cues. Non-circa pacemakers include the heartbeat pacemaker in the sinus node in humans.
Period
The periods of pacemakers range from sub-microsecond in the electric organ of eels (Moortgat, 1998), to 24 hours in circadian pacemakers, to 1 month in the menstrual cycle, to 12 months in hibernation (Fig. 1).
History
The earliest record of an observation of a pacemaker was made by de Mairan, a French astronomer, in 1729 (Hosn, 1997). He observed that clover leaves moved even in total darkness, despite the fact that the purpose of their movement seemed to be to track the sun. Linaeus (1707-1778) introduced the concept of a ‘flower clock’. August Forel (1848-1931) introduced the "time-memory" concept from his study of honey bees (Ward, 1971). In 1914 Szymanski showed that even under constant conditions goldfish had a circadian rhythm. A genetic basis for the circadian rhythms was indicated in experiments in bean plants in 1932. Experiments by showed that the circadian rhythm in Drosophila was temperature compensated (Pittendrigh, 1954). Experiments by Konopka in Benzer’s lab identified a gene in which mutations caused an alteration of the circadian pacemaker’s period, and was thus named Per. Different mutations either shortened or lengthened the period, or abolished the rhythm altogether (Chandrashekaran, 1999). Since then many other genes involved in circadian pacemaker have been identified (see below).
Although pacemakers have only been studied recently (since the 18th century), the biological rhythms that pacemakers control are mentioned in the Bible (Psalms) and in the writings of Aristotle (384-322 BC) (Ward, 1971), and the human heartbeat has surely been known to humans for as long as we have existed (130,000 years of anatomically modern humans).
Mechanisms
Oscillatory processes that underlie sensory coding, attention, memory and sleep (Fontanini, 2006).
Artificial pacemakers
Artificial pacemakers are used to rescue patients with deficient pacemakers, for example when the sinus node of the heart does not function correctly. Genetically engineered pacemakers may begin to replace microelectronic pacemakers (Boink, 2006). Micoelectronic pacemakers implanted in the brain of epilepsy patients at the precise (with 1 mm accuracy) locations that are the origins of seizures in a given patient create signals that help prevent seizures (http://www.clevelandclinic.org/health/health-info/docs/1900/1937.asp?index=8782).
References
Boink GJ, Seppen J, de Bakker JM, Tan HL (2006) .Gene therapy to create biological pacemakers.Med Biol Eng Comput. Oct 18; [Epub ahead of print]
Fontanini A, Bower JM.Slow-waves in the olfactory system: an olfactory perspective on cortical rhythms.Trends Neurosci. 2006 Aug;29(8):429-37. Epub 2006 Jul 13.
Moortgat KT, Clifford H. Keller§, Theodore H. Bullock, and Terrence J. Sejnowski (1998) Submicrosecond pacemaker precision is behaviorally modulated: The gymnotiform electromotor pathway. PNAS Vol. 95, Issue 8, 4684-4689.
