BIO254:Pacemaker

Due Date: 11/20

Pacemaker

A pacemaker is a biological oscillator (biological clock, biological timer). Pacemakers control the timing of many biological processes or functions including sleep, the menstrual cycle, and hybernation. The field of biology that studies pacemakers is chronobiology.

Temporal Range

The periods of pacemakers range from sub-microsecond in the electric organ of eels (Moortgat, 1998), to 24 hours in the circadian rhythm, to 1 month in the menstrual cycle, to 12 months in hybernation. There may be longer cycles: for example the progression from sexual immaturity to reproductive competence to menopause in women can be considered a single cycle of a biological clock.

File:Buhusi2005Fig1.tif

Figure 1. Image from (Buhusi, 2006).

Mechanisms

Pacemakers use various mechanisms to keep track of time, and control many different biological functions. Here we will focus on pacemakers involved in the nervous system.

and functions of neurobiological pacemakers=

Oscillatory processes that underlie sensory coding, attention, memory and sleep (Fontanini, 2006).

 Biological pacemakers drive many time-dependent processes in organisms, including heart rate, cell division in embryogenesis, and circadian activities.  

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).

Biological pacemakers can be in a single cell, but typically involve many cells. The periods of biological pacemakers span a large range.

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.

Heterotrimeric G proteins

Heterotrimeric G proteins are comprised of three subunits -- α, β and γ -- that exist as a complex (G_αβγ) in the GDP-bound state but dissociate (into G_α and G_βγ) upon the release of GDP and binding of GTP. G_α contains the GDP/GTP binding site and GTPase activity (Fig. 1). The C-terminus of G_α gives the G protein affinity for specific membrane-bound GPCRs (see below).

Figure 1. Image from (Milligan, 2006). Some parts have been removed for clarity. GDP is shown in purple. The α subunit C-terminus residues, shown in blue, convey GPCR specificity. The N-terminus helix, shown in red, is required for binding of G_αto the other subunits.

A pacemaker (in the context of NBIO 254) is a biological clock, or in other words a rhythm generator in an organism.

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