Download Agrin regulates beat frequency of cardiac myocytes

11211
Agrin Regulates Beat Frequency of Cardiac Myocytes
Saif Liswi
Mentor: Diane O’Dowd
Each year, millions of people die from heart disease and cardiac complications. Patients dealing with
irregular heart contractions are prescribed ouabain as a medication to help stabilize their heartbeat.
Ouabain binds to the sodium potassium pump, thereby inhibiting its function. Agrin, an extracellular
matrix protein, has also been shown to bind to and inhibit the subunit of the sodium potassium
pumps ( in neurons. Agrin and the  are expressed in the heart, suggesting that agrin
may also affect cardiac function. To test this hypothesis we cultured cardiac myocytes from
transgenic mice that do not express the agrin gene and found that the mean beat frequency of agrindeficient myocytes was twice as fast as wild type myocytes. Addition of exogenous agrin lowered the
elevated beat frequency in the mutants to wild type levels. Biochemical analysis suggests that agrin,
similar to ouabain directly binds to the and inhibits it. One difference is that agrin
specifically inhibits  activity while ouabain does not discriminate between other  subunits
of NKAs. This is significant because ouabain is a potent drug that must be administered in precise
amounts, as an overdose is toxic. Since agrin is a more specific drug we believe that these findings
have important therapeutic potential.