GABAA Receptor-Mediated Currents and Hormone mRNAs in Cells Expressing More Than One Hormone Transcript in Intact Human Pancreatic Islets

In pancreatic islets, the major cell-types are alpha, beta and delta cells. The gamma-aminobutyric acid (GABA) signalling system is expressed in human pancreatic islets. In single hormone transcript-expressing cells, we have previously characterized the functional properties of islet GABA(A) receptors (iGABA(A)Rs). Here, we extended these studies to islet cells expressing mRNAs for more than one hormone and sought for correlation between iGABA(A)R activity level and relative mRNA expression ratio. The single-cell RT-PCR in combination with the patch-clamp current recordings was used to examine functional properties of iGABA(A)Rs in the multiple hormone mRNA-expressing cells. We detected cells expressing double (alpha/beta, alpha/delta, beta/delta cell-types) and triple (alpha/beta/delta cell-type) hormone transcripts. The most common mixed-identity cell-type was the alpha/beta group where the cells could be grouped into beta- and alpha-like subgroups. The beta-like cells had low GCG/INS expression ratio (<0.6) and significantly higher frequency of iGABA(A)R single-channel openings than the alpha-like cells where the GCG/INS expression ratio was high (>1.2). The hormone expression levels and iGABA(A)R single-channel characteristics varied in the alpha/beta/delta cell-type. Clearly, multiple hormone transcripts can be expressed in islet cells whereas iGABA(A)R single-channel functional properties appear to be alpha or beta cell specific.