TRPC1 is a store-operated cationic channel of the transient receptor potential family. Functionally, TRPC1 is implicated in several physiological roles including endothelial cell permeability, mechanosensitive calcium entry, glutamatergic signalling and smooth muscle cell proliferation. The TRPC1 gene expresses a protein of 793 amino acids, derived from an mRNA transcript of 13 exons. Exon spanning long PCR of TRPC1 in human aorta, saphenous vein, brain and HEK 293 cells was carried out with ethical approval. 11 novel splice variants were sequenced; Exons 2,3, 5, 6, 7, 8 and 9 are all revealed to be cassette exons which can be alternatively spliced. Exon 4 appears to be constitutively spliced, as it is present in all transcripts. In 9 of the variants, splicing events lead to a frameshift deletion and introduction of an early stop codon. Translation of these mRNA transcripts would lead to premature termination and production of a truncated protein. Any truncated protein arising from mRNA containing an early stop codon is potentially harmful to the cell, and nonsense mediated decay (NMD) is a cellular process which has been thought to be in place to degrade aberrant mRNA products containing premature stop codons. Many TRPC1 isoforms identified are potential candidates for NMD. Cycloheximide, an inhibitor of NMD was used to treat HEK 293 cells. Inhibition of NMD increases the stability of transcripts normally degraded by this pathway and this can be detected by PCR and gel electrophoresis. Cycloheximide treated cells showed an increase in the abundance of NMD vulnerable TRPC1 transcripts, indicating alternative splicing of TRPC1 can produce isoforms susceptible to degradation by this pathway. Physiological regulation of TRPC1 splicing was also investigated: HEK 293 cells were store-depleted with thapsigargin and PCR of TRPC1 transcripts six hours later showed an increase in TRPC1 alternative splicing. Exon 4 levels were not changed indicating no alteration of total mRNA turnover. A decrease in the amount of full length TRPC1 and a significant increase in the presence of splice variants, many of which are degraded by NMD was observed. We suggest the alternative splicing and NMD pathways represent a mechanism of regulating TRPC1 dependent calcium entry.